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In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in ‘success’ rate (p= 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p= 0.21). At 24 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p= 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.

The use of molecular beacons is a versatile method to detect RNAs. Typically, a single-stranded region of RNA is selected as a target sequence for molecular beacons. Therefore, the detection of highly structured short RNAs, such as tRNAs, seems to be difficult. In this study, as an example of highly structured target RNA, we used human tRNALys3, which is known to have functions in protein synthesis and the reverse transcription of human immunodeficiency virus (HIV)-1. No long single-stranded region more than 8 nt is present in this tRNA, which is much shorter than the standard target length of molecular beacons (∼20 nt). This study showed that sensitive detection of highly structured RNAs using molecular beacons was much more difficult than that of unstructured or less structured RNAs. However, efficient detection of the tRNALys3was achieved by selecting the best target region, i.e., the region around the D arm, probably due to the ease of unfolding of this arm. Accordingly, our findings suggested that molecular beacons may have applications in the detection of highly structured RNAs related to various biological functions and diseases.

Recently, two genome-wide association studies (GWASs) of schizophrenia (SCZ) in Han Chinese identified several susceptibility loci. Replication efforts aiming to validate the GWAS findings were made and focused on the top hits. We conducted a more extensive follow-up study in an independent sample of 1471 cases and 1528 matched controls to verify 26 genetic variants by including nine top single-nucleotide polymorphisms (SNPs) that reached genome-wide significance and 17 promising SNPs nominated in the initial discovery phase. rs8073471 in an intron of tubulin-folding cofactor D (TBCD) obtained nominal significance (P<0.01) in single SNP analysis. Logistic regression identified significant interaction between rs3744165 (5’-untranslated region variant of exon 2 of zinc finger protein 750 (ZNF750), and in an intron of TBCD) and rs8073471 (Deviance test P-value=2.77 × 10-34). Both SNPs are located at 17q25, an interesting region that has been implicated in SCZ. By using the Genotype-Tissue Expression (GTEx) data set, we implemented an expression quantitative trait loci epistasis analysis to explore the association between the genotype combinations of the two SNPs and gene expression levels in 13 areas of human central nervous system. We observed that rs3744165 × rs8073471 interaction modulated the expression profile of TEAD3 (P=1.87 × 10-8), SH3TC2 (P=2.00 × 10-8), KCNK9 (P=5.20 × 10-7) and PPDPF (P=1.13 × 10-6) in postmortem cortex tissue; EFNA1 (P=7.26 × 10-9), RNU4ATAC (P=2.32 × 10-8) and NUPL2 (P=6.79 × 10-8) in cerebellum tissue. To the best of our knowledge, our study is the first one that links TBCD and ZNF750 mutations to SCZ susceptibility and to the transcript levels in human brain tissues. Further efforts are needed to understand the role of those variants in the pathogenesis of SCZ.

Dark-field images are formed from x-ray small-angle scattering signals. The small-angle scattering signals are particularly sensitive to structural variation and density fluctuation on a length scale of several tens to hundreds of nanometers, offering a unique contrast mechanism to reveal subtle structural features of an object. In this study, based on the principle of energy conservation, we develop a physical model to describe the relationship between x-ray small-angle scattering coefficients of an object and dark-field intensity images. This model can be used to reconstruct volumetric x-ray small-angle scattering images of an object using classical tomographic algorithms. We also establish a relationship between the small-angle scattering intensity and the visibility function measured with x-ray grating imaging. The numerical simulations and phantom experiments have demonstrated the accuracy and practicability of the proposed model.

Fluid flow and particle collision intensity in a rotating‐drum bioreactor are investigated by numerical simulation and a conventional stirred‐tank bioreactor is selected for comparison. Fluid flow is simulated by the computational fluid dynamics (CFD) software package FLUENT® whereas particle collision intensity is approached numerically through a hard‐sphere model. The dissipation rate of turbulent kinetic energy and the maximum particle collision intensity in the rotating‐drum bioreactor are about one order of magnitude smaller than those in the stirred‐tank bioreactor. The rotating‐drum bioreactor is likely to have a less severe impact on bioleaching microorganisms, and thus is expected to have great potential in the field of bioleaching processes.

A reconstruction method of bioluminescence sources is proposed based on a phase approximation model. Compared with the diffuse approximation, this phase approximation model more correctly predicts bioluminescence photon propagation in biological tissues, so that bioluminescence tomography can accurately locate and quantify the distribution of bioluminescence sources. The compressive sensing (CS) technique is applied to regularize the inverse source reconstruction to enhance numerical stability and efficiency. The numerical simulation and phantom experiments demonstrate the feasibility of the proposed approach.

： In this work, the effect of temperature on the microstructure evolution of vacuum brazed joint of TiAl alloy and 42CrMo was studied. The results have shown when the brazing temperature is under 870℃, no compound is formed at the boundary on the 42CrMo side. But when brazing temperature is over 870℃, a very narrow TiC compound film is found at the homologous site., while on the TiAl side, there always exists a Ti(Cu,Al)2 intermetallic compound layer at any brazing temperature. The elemental diffusion and reaction is the predominant factor of joint forming. The tensile fracture strength of brazed joint increases with the brazing temperature, the increase of the tensile strength of joint is due to the variation of the joint structure.

We present a generalized delta-Eddington phase function to simplify the radiative transfer equation to an integral equation with respect to the photon flux vector. The solution of the integral equation is highly accurate to model the photon propagation in the biological tissue over a broad range of optical parameters, especially in the visible light spectrum where the diffusion approximation breaks down. The methodology is validated in the Monte Carlo simulation and can be applied in various optical imaging applications.

Marine propellers with complex shaped surface could not satisfy hydrodynamics and have complex flow-structure interactions during running. While cavitation and marine organisms are two obstacles when ship propellers keep propulsion efficiency, many of them have been coated with fouling release coating to maintain propeller propulsion efficiency. In this paper, the introduction of the composite coating to marine propellers can not only effectively resist to cavitation erosion, but also be free from marine organisms. In the above context, tests for the cavitation characteristics of the composite coating were carried out. Composite coatings on the tool head for 40 h or hedging for 100 h had slightly loss of light with the cumulative weight loss less than 5 mg. Open water tests showed the composite coating did not significantly affect thrust and torque characteristics of model propeller. After the use on ship propellers for a period of 16 months, composite coating matched well only with minor damage on the leading edge, but none diffusion under the coating layer. And also marine organisms on blades of propeller could be washed away easily with high pressure water.

Under static conditions, fouling release coating could not express good release property to marine organisms. Amphiphilic polymer with mixture of fluorinated monomer and short side group of polyethylene glycol (PEG) was synthesized. And also we studied the ability of amphiphilic polymer to influence the surface properties and how it controlled the adhesion of marine organisms to coated surfaces. By incorporating fluorinated monomer and PEG side chain into the polymer, the effect of incorporating both polar and non-polar groups on fouling-release coating could be studied. The dry surface was characterized by three-dimensional digital microscopy and scanning electron microscopy (SEM), and the morphology of the amphiphilic fouling release coating showed just like flaky petal. The amphiphilic polymer in fouling release coating tended to reconstruct in water, and the ability was examined by static contact angle, which was smaller than the PDMS (polydimethylsiloxane) fouling release coating. Also surface energy was calculated by three solvents, and surface energy of amphiphilic fouling release coating was higher than that of the PDMS fouling release coating. To understand more about its fouling release property, seawater exposure method was adopted in gulf of Qingdao port. Fewer diatoms Navicula were found in biofilm after using amphiphilic fouling release coating. In general, coating containing both PEG and fluorinated side chain possessed certain fouling release property.

A high-fibre diet and one rich in fruit and vegetables have long been associated with lower risk of chronic disease. There are several possible mechanisms underpinning these associations, but one likely important factor is the production of bioactive molecules from plant-based foods by the bacteria in the colon. This links to our growing understanding of the role of the gut microbiome in promoting health. Polyphenolic-rich plant foods have been associated with potential health effects in many studies, but the bioavailability of polyphenol compounds, as eaten, is often very low. Most of the ingested molecules enter the large intestine where they are catabolised to smaller phenolic acids that may be the key bioactive effectors. Dietary fibres, present in plant foods, are also fermented by the bacteria to short-chain fatty acids, compounds associated with several beneficial effects on cell turnover, metabolism and eating behaviour. Polyphenols and fibre are often eaten together, but there is a lack of research investigating the interaction between these two groups of key substrates for the colonic bacteria. In a project funded by the Biotechnology and Biological Sciences Research Council Diet and Health Research Industry Club, we are investigating whether combining different fibres and polyphenol sources can enhance the production of bioactive phenolic acids to promote health. This could lead to improved dietary recommendations and to new products with enhanced potential health-promoting actions.