Cinnamaldehyde attenuates streptozocin-induced diabetic osteoporosis in a rat model by modulating netrin-1/DCC-UNC5B signal transduction

Background: Cinnamaldehyde (CMD) is a major functional component of Cinnamomum verum and has shown treatment effects against diverse bone diseases. This study aimed to assess the anti-diabetic osteoporosis (DOP) potential of diabetes mellitus (DM) and to explore the underlying mechanism driving the activity of CMD.Methods: A DOP model was induced via an intraperitoneal injection of streptozocin (STZ) into Sprague–Dawley rats, and then two different doses of CMD were administered to the rats. The effects of CMD on the strength, remodeling activity, and histological structure of the bones were assessed. Changes in the netrin-1 related pathways also were detected to elucidate the mechanism of the anti-DOP activity by CMD.Results: CMD had no significant effect on the body weight or blood glucose level of the model rats. However, the data showed that CMD improved the bone strength and bone remodeling activity as well as attenuating the bone structure destruction in the DOP rats in a dose-dependent manner. The expression of netrin-1, DCC, UNC5B, RANKL, and OPG was suppressed, while the expression of TGF-β1, cathepsin K, TRAP, and RANK was induced by the STZ injection. CMD administration restored the expression of all of these indicators at both the mRNA and protein levels, indicating that the osteoclast activity was inhibited by CMD.Conclusion: The current study demonstrated that CMD effectively attenuated bone impairments associated with DM in a STZ-induced DOP rat model, and the anti-DOP effects of CMD were associated with the modulation of netrin-1/DCC/UNC5B signal transduction

The efficacy and safety of different Janus kinase inhibitors as monotherapy in rheumatoid arthritis: A Bayesian network meta-analysis.

ObjectiveThis study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA.MethodsThe databases CNKI, VIP, Wanfang, CBM, and PubMed, Embase, Cochrane Library and Web of Science were searched to identify relevant randomized controlled trials (RCTs), all from the time of database creation to April 2024. Screening, data extraction, and risk of bias assessment (using Review Manager-5.3 software) were independently performed by at least two authors. The network meta-analysis was conducted using R 4.1.3 software. PROSPERO registration number: CRD42022370444.ResultsThirty-three RCTs included 15,961 patients The experimental groups involved six JAK inhibitors (filgotinib, tofacitinib, decernotinib, baricitinib, upadacitinib and peficitinib) and 12 interventions (different doses of the six JAK inhibitors), and the control group involved adalimumab (ADA) and placebo. Compared with placebo, all JAK inhibitors showed a significant increase in efficacy measures (ACR20/50/70). Compared with ADA, only tofacitinib, low-dose decernotinib, and high-dose peficitinib showed a significant increase in ACR20/50/70. Decernotinib ranked first in the SUCRA ranking of ACR20/50/70. In terms of safety indicators, only those differences between low-dose filgotinib and high-dose upadacitinib, low-dose tofacitinib and high-dose upadacitinib were statistically significant. Low-dose filgotinib ranked first in the SUCRA ranking with adverse events as safety indicators. Only the efficacy and safety of tofacitinib ranked higher among different SUCRA rankings.ConclusionSix JAK inhibitors have better efficacy than placebo. The superior efficacy of decernotinib and safety of low-dose filgotinib can be found in the SUCRA. However, there are no significant differences in safety between the different JAK inhibitors. Head-to-head trials, directly comparing one against each other, are required to provide more certain evidence

Coupled effect of Ag and In addition on the microstructure and mechanical properties of Sn–Bi lead-free solder alloy

The microstructure and mechanical properties of Sn–Bi solder alloys with various Ag and In addition are comparatively investigated. The results illustrate that the tensile strength and ductility of the solder alloy could be dramatically enhanced with negligible loss of the plasticity. Especially, the Sn–Bi solder alloy with 0.4 wt. % Ag and 1.5 wt. % In exhibits the maximum tensile strength and elongation of 79.7 MPa and 45.9%, respectively. The microstructure of the Sn–Bi solder alloys is mainly composed of Bi-rich and β-Sn phases. With the addition of elements Ag and In, the microstructure is significantly refined, and the lamellar eutectic structure with thinner interlayer spacing could be detected. Element Ag tends to form Ag3Sn phase while element In solutes in the Sn matrix. The mechanical properties of the as-prepared Sn–Bi solder alloy are improved attributed to the precipitated-phase strengthening of the fined Ag3Sn phase and the refinement effect of In on coarse Bi-rich phase

Realization of minute-long steady-state H-mode discharges on EAST

In the 2016 EAST experimental campaign, a steady-state long-pulse H-mode discharge with an ITER-like tungsten divertor lasting longer than one minute has been obtained using only RF heating and current drive, through an integrated control of the wall conditioning, plasma configuration, divertor heat flux, particle exhaust, impurity management, and effective coupling of multiple RF heating and current drive sources at high injected power. The plasma current (I p ~ 0.45 MA) was fully-noninductively driven (V loop < 0.0 V) by a combination of ~2.5 MW LHW, ~0.4 MW ECH and ~0.8 MW ICRF. This result demonstrates the progress of physics and technology studies on EAST, and will benefit the physics basis for steady state operation of ITER and CFETR