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Rheumatoid arthritis (RA) is a heterogeneous chronic disease. RA patients should start disease modifying anti-rheumatic drugs (DMARDs) therapy immediately after diagnosis. If first-line treatment with conventional synthetic DMARDs does not relieve the disease, biology and targeted synthetic DMARDs are options for patients. Patients can switch to different types of biological and targeted synthetic DMARDs if remission is not achieved. However, for patients with difficult-to-treat RA, achieving disease stabilization after the failure of multiple biological and targeted synthetic DMARDs is a clinical challenge that needs to be addressed. As distinct cytokine pathways, the benefits and challenges of dual therapy are worth discussing. As the most extensively used biologic DMARDs, adalimumab is an anti-tumor necrosis factor monoclonal antibody used to treat RA. Tofacitinib, as a Janus Kinase inhibitor, is an orally administered targeted synthetic DMARDs that involved in the regulation of immune responses by directly or indirectly inhibiting cytokine pathways. This report describes a successful case of a 48-year-old woman with difficult-to-treat RA who treated with Tofacitinib combined with adalimumab. She had been on glucocorticosteroid for a long time, but had persistent joint pain and fatigue. At more than one year of follow-up, her Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-ESR) remained in complete remission, and she discontinued her glucocorticosteroid medications. Also, she did not develop a mycobacterial tuberculosis infection, herpes zoster, and new-onset cardiovascular events.

Background: Traditional thyristor-based three-phase soft starters of induction motor often suffer from high starting current and heavy harmonics. Moreover, both the trigger pulse generation and driving circuit design are usually complicated. Methods: To address these issues, we propose a novel soft starter structure using fully controlled IGBTs in this paper. Compared to approaches of traditional design, this structure only uses twophase as the input, and each phase is controlled by a power module that is composed of one IGBT and four diodes. Results: Consequently, both driving circuit and control design are greatly simplified due to the requirement of fewer controlled power semiconductor switches, which leads to the reduction of the total cost. Conclusion: Both Matlab/Simulink simulation results and experimental results on a prototype demonstrate that the proposed soft starter can achieve better performances than traditional thyristorbased soft starters for Starting Current (RMS) and harmonics.

One key feature of the interaction of Flp recombinase with its target site ( FRT ) is the large bend introduced in the substrate as a result of protein binding. The extent of bending was found to depend on the phasing and spacing of the Flp monomers occupying the two Flp-binding elements ( FBE ) bordering the strand-exchange region (spacer) of the substrate. The relative mobilities of the Flp complexes formed by the two permuted substrate fragments, containing the FRT site near the end or in the middle, corresponded to a DNA bend of approx. 140° when each of the two FBE s flanking the spacer was occupied by a protein monomer. The estimated bend angle was the same when the reference DNA fragment with the FRT site at the end was substituted by one with the site in the middle, but containing a 4-bp insertion within the spacer. We used a combination of wild-type Flp and Flp variants that were competent or incompetent in DNA bending, together with full, or half FRT sites, to ask whether bending is a conformational requirement for catalysis, namely cleavage and exchange of strands. We obtained the following results: in full-site ( FRT ) vs. full-site recombinations or in full-site vs. half-site (half FRT ) recombinations, there was a large difference in the reactivity between Flp and a bending-incompetent Flp variant. This difference virtually disappeared when reactions were done with half- FRT sites. We conclude that bending is not a prerequisite for catalysis, but represents the manner in which the substrate accommodates the Flp protomer-protomer interactions that are pertinent to catalysis.

The essential oil of Marchantia convoluta was obtained by supercritical (carbon dioxide) extraction using methanol as a modifier. Global yields were determined according to the orthogonal design. The effects of different parameters, such as pressure, temperature, modifier volume and extraction time, on the supercritical fluid extraction (SFE) of essential oil from M. convoluta were investigated. Maximum global yields were obtained using the following conditions: extraction temperature, 35ºC; dynamic time, 35 min; pressure, 15 Mpa and modifier volume, 40 mL. The essential oil extract was analyzed by capillary gas chromatography with mass spectrometric detector (GC-MS). The compounds were identified according to their retention indices and mass spectra (EI, 70 eV). The results from GC-MS and literature were compared.