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Abstract Aims The long‐term cost‐effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long‐term cost‐effectiveness of MitraClip added to guideline‐directed medical therapy vs. guideline‐directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. Methods and results A two‐stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re‐hospitalization, and death and were calculated based on the 5 year follow‐up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country‐specific rates. The primary outcome was the lifetime incremental cost‐effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re‐hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality‐adjusted life‐year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost‐effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality‐adjusted life‐year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost‐effective in mainland China, the United Kingdom, Germany, and the United States at the country‐specific willingness‐to‐pay thresholds. Conclusions MitraClip + guideline‐directed medical therapy was cost‐effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Abstract The main protease (Mpro) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized Mpro showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. Mpro forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein’s crystallization behavior is linked to its redox state. Oxidized Mpro spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of Mpro and the crystallization conditions necessary to study this structurally.

Abstract Background The prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age. Methods A total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were selected and divided into the younger group (

The paper adopts the architecture of "ADC+FPGA", designs and develops a 1 GS/s, 16-bit high-speed and high-precision data acquisition system(DAS), which realized the purpose of using a single channel to measure large dynamic range(DR>1 000) signals. The study uses two sysref modes, which are periodic sysref mode and pulse sysref mode, to establishe a stable JESD204B link with a deterministic delay. The differences in the sampled data spectrum between the two modes is presented, and the considerations of hardware design and firmware design are given. The paper recommends that the periodic sysref mode be used to establish JESD204B link. By analyzing the time-domain waveform and frequency spectrum of the sampled data, the conclusion that the ADC chip contains 4 on-chip ADC channels is verified.

Long-wavelength pulses from the Swiss X-ray free-electron laser (XFEL) have been used for de novo protein structure determination by native single-wavelength anomalous diffraction (native-SAD) phasing of serial femtosecond crystallography (SFX) data. In this work, sensitive anomalous data-quality indicators and model proteins were used to quantify improvements in native-SAD at XFELs such as utilization of longer wavelengths, careful experimental geometry optimization, and better post-refinement and partiality correction. Compared with studies using shorter wavelengths at other XFELs and older software versions, up to one order of magnitude reduction in the required number of indexed images for native-SAD was achieved, hence lowering sample consumption and beam-time requirements significantly. Improved data quality and higher anomalous signal facilitate so-far underutilized de novo structure determination of challenging proteins at XFELs. Improvements presented in this work can be used in other types of SFX experiments that require accurate measurements of weak signals, for example time-resolved studies.

Hot deformation is a way to effectively improve strength and plasticity of multiphase steels simultaneously, thereby, improving mechanical properties of multiphase steels. Hot deformation affects martensitic transformation mechanism, microstructure, and mechanical properties because it increases retained austenite content and improves stability of multiphase steels. Moreover, hot deformation plays a role in dislocation multiplication, and fine grain strengthening; it can reduce bainite transformation driving force, reduce bainite transformation point, and result in small multiphase organization after quenching-partitioning process. The result can significantly improve the properties of materials. The effects of high-temperature deformation on the stability of room-temperature microstructure, mechanical property, and retained austenite under treatment of IQ&PB (intercritical annealing-quenching and partitioning within the bainitic region) and DIQ&PB (intercritical deformation-intercritical annealing-quenching and partitioning within the bainitic region) processes were studied using scanning electron microscopy (SEM), transmission electron microscope (TEM), electron probe X-ray microanalyser (EPMA), X-ray diffraction (XRD), and tensile testing machine. The results show that dislocation density increases from 0.290×1014 to 1.286×1014 m-2 after 15% compression deformation, and the respective concentrations of C and Cu element enrichment in martensite (the original austenite) increases. Overall, dislocation multiplication produced by high-temperature deformation significantly promotes elemental distribution. After the deformation, the size of bainite lath shortenes and its width increases by 0.1 μm, the volume of the bainite transition increased by 14%, and the size of the polygonal ferrite significantly decreases under the DIQ&PB treatment. In terms of mechanical properties, the tensile strength increases by 132.85 MPa, and the elongation increases by 7%; the strength and ductility product reaches 25435 MPa·% after intercritical deformation heat treatment. The volume fraction of retained austenite increases from 7.8% to 8.99%, and the mass fraction of carbon in the retained austenite increases from 1.05% to 1.31% after compression deformation.

Serial crystallography was developed for protein crystal data collection with X-ray free-electron lasers. Here the authors present several examples which show that serial crystallography using high-viscosity injectors can also be routinely employed for room-temperature data collection at synchrotrons.

SiO2 gel/alumina-silica fibers composites were prepared by impregnation method. Silicon powder with different mass fractions of 0%, 0.2%, 0.4%, 0.6% and 0.8% was added in the slurry, and the effects of silicon powder on the microstructure, bulk density, compression-resilience ratio and phase compositions of the SiO2 gel/alumina-silica fiber composites were investigated. The results show that when the mass fraction of the silicon powder is lower than 0.6%, the volume expansion of silicon resulting from the silicon oxidation fills the cracks between fibers and gel, the volume density of the composites increases from 0.468g/cm3 to 0.723g/cm3, and the resilience ratios increase from 43.1% to 59.6%. Besides, it is found that the mechanical property is improved and the degree of high-temperature damage for the composites is decreased by the silicon crystallization, which restrains the fibers crystallization and facilitates the generation of pyroxene. However, when the mass fraction of silicon powder is 0.8%,the compression-resilience ratio of the composites significantly declines to 44.5%, which is attributed to the big cracks generated from the excessive volume expansion of silicon powder at high temperature.