Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/β-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/β-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-α, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-κB p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-κB and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.

Cystic echinococcosis (CE) occurs in the intermediate host's liver, assuming a bladder-like structure surrounded by the host-derived collagen capsule mainly derived from activated hepatic stellate cells (HSCs). However, the effect of CE on liver natural killer (NK) cells and the potential of transforming growth factor-β (TGF-β) signalling inhibition on alleviating CE-related liver damage remain to be explored. Here, by using the CE-mouse model, we revealed that the inhibitory receptors on the surface of liver NK cells were up-regulated, whereas the activating receptors were down-regulated over time. TGF-β1 secretion was elevated in liver tissues and mainly derived from macrophages. A combination of TGF-β signalling inhibitors SB525334 and pirfenidone could reduce the expression of TGF-β1 signalling pathway-related proteins and collagen production. Based on the secretion of TGF-β1, only the pirfenidone group showed a depressing effect. Also, the combination of SB525334 and pirfenidone exhibited a higher potential in effectively alleviating the senescence of the hepatocytes and restoring liver function. Together, TGF-β1 may be a potential target for the treatment of CE-associated liver fibrosis.

The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13–3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95–5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66–3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80–24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87–2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Recently, the asymptotic mean value of the height for a birth-and-death process is given in Videla [Videla, L.A. (2020)]. We consider the asymptotic variance of the height in the case when the number of states tends to infinity. Further, we prove that the heights exhibit a cutoff phenomenon and that the normalized height converges to a degenerate distribution.

OBJECTIVES/SPECIFIC AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative procedure for hematological malignancies. Chronic graft Versus host disease (cGVHD) is a lethal complication that often develops after allo-HCT. Fli-1 is an aberrantly expressed protein in cancers including erythroleukemia and melanoma, while being implicated in pathogenesis of systemic lupus in mice and humans, a disease with marked similarity to cGVHD. METHODS/STUDY POPULATION: cGVHD was induced using hematopoietic cells from conditional knock-out mice deficient for the fli-1 gene specifically on T cells and progression of cGVHD in murine allo-HCT recipients was monitored using a clinical scoring system, and changes in activation status of hematopoietic cell populations were quantified using flow cytometry. RESULTS/ANTICIPATED RESULTS: Recipients transplanted with fli-1 deficient T cells exhibited reduced cGVHD clinical scores compared with littermate wild-type controls. Donor-grafts containing fli-1 deficient T cells were associated with restrained T-cell responses including reduced Interferon-y cytokine production, PD-1 expression, and differentiation into follicular helper T cells. fli-1 T-cell deficient donor-grafts also improved donor B-cell reconstitution and reduced plasma cells in allo-HCT recipients relative to littermate wild-type control donor-graft recipients. DISCUSSION/SIGNIFICANCE OF IMPACT: Thus, inhibiting Fli-1 represents a promising therapeutic strategy for the goal of preventing cGVHD after allo-HCT while also directly targeting cancers which aberrantly express Fli-1.

This paper presents a binocular vision-IMU (Inertial Measurement Unit) tightly-coupled structure based on a Minimum sigma set Square-Root Unscented Kalman Filter (M-SRUKF) for real time navigation applications. Though the M-SRUKF has only half the sigma points of the SRUKF, it has the same accuracy as the SRUKF when applied to the binocular vision-IMU tightly-coupled system. As the Kalman filter flow is a kind of square-root system, the stability of the system can be guaranteed. The measurement model and the outlier rejection model of this tightly-coupled system not only utilises the epipolar constraint and the trifocal tensor geometry constraint between the consecutive two image pairs, but also uses the quadrifocal tensor geometry among four views. The structure of the binocular vision-IMU tightly-coupled system is in the form of an error state, and the time updates of the state and the state covariance are directly estimated without using Unscented Transformation (UT). Experiments are carried out based on an outdoor land vehicle open source dataset and an indoor Micro Aerial Vehicle (MAV) open source dataset. Results clearly show the effectiveness of the proposed new mechanisation.

Little published information is available related to seed germination and seedling establishment of Asia Minor bluegrass, a problematic grass weed in some regions of China. The objective of this study was to examine the effects of different environmental factors on Asia Minor bluegrass seed germination. The optimum temperature for germination was around 10 to 20 C, and more than 90% of seeds germinated under 20/10 and 25/15 C temperature regimes. Also, light and pH did not appear to have any effect on seed germination. Asia Minor bluegrass was sensitive to osmotic stress, but tolerant of NaCl. No seedlings emerged when seeds were buried 4 cm deep. The result suggested that Asia Minor bluegrass has the potential to spread into a large area in China. To prevent its spreading, measures such as soil cultivation can be used to limit seed germination from increased burial depth and/or nonselective herbicides can be applied to kill early-germinating weed seedlings in late summer.

Tributyltin, an organotin, is ubiquitous in estuaries and freshwater systems. Previous reports suggest that tributyltin is an endocrine disruptor in many wildlife species and it inhibits aromatase in mammalian placental and granulosa-like tumor cell lines. However, no evidence showing the effects of tributyltin on oocytes or preimplantation embryonic developmental competence exists. Therefore, we investigated the role of tributyltin chloride (TBTCl) in the development of female oocytes and preimplantation embryos. Briefly, female ICR mice were gavaged with 0 (vehicle), 4, and 8 mg/kg of TBTCl each day for 18 days. The fluorescence intensity analysis showed that the 5-methylcytosine level decreased after TBTCl treatment, indicating that the general DNA methylation level decreased in the treated oocytes. Our results demonstrate that TBTCl treatment results in decreased mRNA levels of imprinted genes H19, Igf2r, and Peg3 during oocyte growth. The TBTCl-treated oocytes showed a significant increase in reactive oxygen species levels in germinal vesicle oocytes. In TBTCl-treated oocytes, there was no difference in GPx and Sod1 expression, but a decreased mRNA level of Cat occurred when compared with control. Moreover, the blastocysts with TBTCl exposure displayed higher apoptotic signals. These results suggest that TBTCl induces developmental defects in oocytes and preimplantation embryos.

We use detrital provenance data from Cambrian sandstones to examine whether the Yangtze and Cathaysia blocks in South China were separated by an ocean during the Cambrian period. Zircons from the Cambrian sandstones exhibit a dominant ~ 800 Ma age peak in the central Yangtze Block, being sourced from the western Yangtze Block, whereas a ~ 980 Ma peak dominates in the northwestern Cathaysia Block, being sourced from an exotic continent once connected to Cathaysia. A mixed provenance with both age peaks is found in Cambrian sandstones from the southeastern Yangtze Block, indicating that detritus can travel from the Cathaysia Block to the Yangtze Block, and therefore arguing against the existence of a broad Cambrian ocean.

We review the present status and future prospects of fast ignition (FI) research of the theoretical group at the IAPCM (Institute of Applied Physics and Computational Mathematics, Beijing) as a part of the inertial confinement fusion project. Since the approval of the FI project at the IAPCM, we have devoted our efforts to improving the integrated codes for FI and designing advanced targets together with the experimental group. Recent FI experiments [K. U. Akli et al., Phys. Rev. E 86, 065402 (2012)] showed that the petawatt laser beam energy was not efficiently converted into the compressed core because of the beam divergence of relativistic electron beams. The coupling efficiency can be improved in three ways: (1) using a cone–wire-in-shell advanced target to enhance the transport efficiency, (2) using external magnetic fields to collimate fast electrons, and (3) reducing the prepulse level of the petawatt laser beam. The integrated codes for FI, named ICFI, including a radiation hydrodynamic code, a particle-in-cell (PIC) simulation code, and a hybrid fluid–PIC code, have been developed to design this advanced target at the IAPCM. The Shenguang-II upgraded laser facility has been constructed for FI research; it consists of eight beams (in total $24~ {\rm kJ}/3\omega $, 3 ns) for implosion compression, and a heating laser beam (0.5–1 kJ, 3–5 ps) for generating the relativistic electron beam. A fully integrated FI experiment is scheduled for the 2014 project.

The spin Hamiltonian parameters (g factor and hyperfine structure constants) of Cr+ in ZnX (X = S, Se, Te) and CdTe are theoretically investigated, using the perturbation formulas of these parameters for a tetrahedral 3d5 cluster. Both the contributions from the crystal-field (CF) and charge transfer (CT) mechanisms are considered from the cluster approach. The calculated results show good agreement with the experimental data. The CT contribution to g-shift Δg (=g − gs, where gs =2.0023 is the spin only value) is opposite (positive) in sign related to the CF one, and its importance (characterized by the relative ratio (|ΔgCT/ΔgCF|) is 11%, 66% and 104% (71%) for ZnS, ZnSe and ZnTe (CdTe), respectively. ACT from the CT contribution to hyperfine structure constant is the same (positive) in sign and about 50–53% in magnitude as compared with ACF from the CF one.

Bandit processes and the Gittins index have provided powerful and elegant theory and tools for the optimization of allocating limited resources to competitive demands. In this paper we extend the Gittins theory to more general branching bandit processes, also referred to as open bandit processes, that allow uncountable states and backward times. We establish the optimality of the Gittins index policy with uncountably many states, which is useful in such problems as dynamic scheduling with continuous random processing times. We also allow negative time durations for discounting a reward to account for the present value of the reward that was received before the present time, which we refer to as time-backward effects. This could model the situation of offering bonus rewards for completing jobs above expectation. Moreover, we discover that a common belief on the optimality of the Gittins index in the generalized bandit problem is not always true without additional conditions, and provide a counterexample. We further apply our theory of open bandit processes with time-backward effects to prove the optimality of the Gittins index in the generalized bandit problem under a sufficient condition.

The intensity of pupal diapause in the cotton bollworm, Helicoverpa armigera (Hübner) was investigated under both laboratory and natural conditions. By transferring diapausing pupae induced under LD 11:13, LD 12:12 and LD 13:11 at 20, 22 and 25 °C to 25 °C combined with LD 15:9 to terminate diapause the rearing day length of 11 h evoked greater intensity of diapause than did 12 and 13 h at 25 °C; whereas the rearing temperature of 25 °C evoked more intense diapause than did 20 and 22 °C under LD 11:13. By transferring diapausing pupae induced under LD 12:12 at 20 and 22 °C to six temperatures of 18, 20, 22, 25, 28 and 31 °C combined with LD 15:9 to terminate diapause, the duration of diapause was significantly shortened from 146 days at 18 °C to 24 days at 31 °C, showing that high temperatures significantly accelerate diapause development. Furthermore, the duration of diapause was significantly longer at the rearing temperature of 22 °C than that at 20 °C when the diapause-terminating temperatures were 20 and 22 °C. Chilling at 5 °C did not shorten the duration of diapause but lengthened it when chilling period was included. However, chilling plays an important role in synchronizing adult emergence. Rearing temperature of 22 °C also evoked more intense diapause than did 20 °C in most chilling treatments. When the overwintering pupae were transferred at different times from natural temperatures to 25 °C, it was found that the earlier the transfer took place, the earlier the adults emerged when the time spent under natural conditions was included. However, cool temperatures before March showed an enhanced effect on diapause development at 20 °C, suggesting that the high diapause-terminating temperature can offset the effect of chilling on diapause development. The result of diapause termination under natural conditions suggests that the developmental threshold for post-diapause development in H. armigera should be around 17.5 °C.

It has been systematically investigated about the magnetic properties of the composite and single-phase SrFe12O19 prepared with the precursor of different Fe3+/Sr2+ molar ratios of 12:1, 11:1 and 10:1, respectively. With increasing the calcinations temperature, the coercivity of all samples decreases which can be determined by the stress model. The δm(H) results indicate that the intergrain exchangecoupling interaction exists both in composite and in single-phase SrFe12O19, resulting in the remanence magnetization enhancement, and the magnetostatic interaction become dominant in the samples with higher calcinations temperatures. The irreversible susceptibilities χirr(H) curves show that there may exhibit the exchange-spring behavior in the composite SrFe12O19 with more soft magnetic γ-Fe2O3, and the irreversible switching field may be qualitatively used to determine the coercivity magnitude.

The period function of Liénard systems ẋ = −y + F(x), ẏ = g(x) associated with a centre is considered and sufficient conditions are presented for the period function to be strictly and globally monotone increasing and to have at least one critical point. Examples of applications and remarks on related work are also given.