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A high incidence of hypersensitivity reactions (HSRs) largely limits the use of paclitaxel injection. Currently, these reactions are considered to be mediated by histamine release and complement activation. However, the evidence is insufficient and the molecular mechanism involved in paclitaxel injection-induced HSRs is still incompletely understood. In this study, a mice model mimicking vascular hyperpermeability was applied. The vascular leakage induced merely by excipients (polyoxyl 35 castor oil) was equivalent to the reactions evoked by paclitaxel injection under the same conditions. Treatment with paclitaxel injection could cause rapid histamine release. The vascular exudation was dramatically inhibited by pretreatment with a histamine antagonist. No significant change in paclitaxel injection-induced HSRs was observed in complement-deficient and complement-depleted mice. The RhoA/ROCK signaling pathway was activated by paclitaxel injection. Moreover, the ROCK inhibitor showed a protective effect on vascular leakage in the ears and on inflammation in the lungs. In conclusion, this study provided a suitable mice model for investigating the HSRs characterized by vascular hyperpermeability and confirmed the main sensitization of excipients in paclitaxel injection. Histamine release and RhoA/ROCK pathway activation, rather than complement activation, played an important role in paclitaxel injection-induced HSRs. Furthermore, the ROCK inhibitor may provide a potential preventive approach for paclitaxel injection side effects.

Previous studies have shown that dietary acid load (DAL) harms bone health, but the evidence is inconsistent and insufficient. This study examined the relationships between DAL and the risk of hip fracture. This case–control study contained 1070 pairs of 1:1 age-, city-, and gender-matched incident cases and controls (mean age, 71 years) recruited in Guangdong, China. Dietary information was collected using a validated 79-item food frequency questionnaire through face-to-face interviews. DAL was estimated based on established algorithms for the potential renal acid load (PRAL) and net endogenous acid production (NEAP). Higher PRAL and NEAP were dose-dependently associated with a higher risk of hip fracture in both the conditional logistic regression model and restricted cubic spline analysis after adjusting for potential covariates. The multivariate-adjusted odds ratios and 95% CI of hip fracture for tertiles 2 and 3 (vs. 1) of DAL were 1.63 (1.18, 2.25) and 1.92 (1.36, 2.71) for PRAL and 1.81 (1.30, 2.53) and 2.55 (1.76, 3.71) for NEAP in all participants (all p-trends < 0.001), respectively. Subgroup analyses showed more pronounced associations in participants with a lower body mass index. Our findings suggested positive associations between the estimated DAL and the risk of hip fractures in the elderly Chinese population.

Filling-to-packing switchover (also called V/P switchover) is critical for assuring injection molding quality. An improper V/P switchover setting may result in various defects of injection-molded parts, such as excessive residual stress, flash, short shot, and warpage, etc. To enhance a consistent molding quality, recent V/P switchover approaches adopt cavity pressure profiles requiring sensors embedded in mold cavities, which is invasive to mold cavities and more expensive. Instead of using cavity pressure sensors, by working with the most popular screw position switchover control, this study hereby proposes a novel approach of tuning V/P switchover timing using a tie-bar elongation profile. In this investigation, a dumbbell testing specimen mold is applied to verify the feasibility of the method proposed. The results show that the mold filling and packing stages can be observed along the tie-bar elongation profile, detected by mounting strain gauges on the tie bars. Also, the characteristics of the cavity pressure are similar to those of the tie-bar elongation profile under a proper clamping force condition. Moreover, the varying process parameter settings which include injection speed, V/P switchover point, and holding pressure, can be reflected in these profiles. By extracting their characteristics, the application of the V/P switchover is proved to be realistic. This research conducted an experiment to verify the proposed V/P switchover decision method based on the tie-bar elongation profile. The result showed that the fluctuation of the part’s weight corresponding to a slight change of the barrel’s temperature from 210 °C to 215 °C can be successfully controlled with this method. Besides, the maximum clamping force increment extracted from the tie-bar elongation profile was found to be a good indicator for online monitoring of the reground material variation.

Amperometric detection of nitric oxide with ISO-NOPMC NO microsensors(WPI) is systemically studied in the six media including seawater. The linear range of themicrosensor for NO was from 10-6 to 10-9 mol/l and the detection limit was4.2×10-10 mol/L(S/N=2). With this method, we provide preliminary evidence that NOproduction could be a general attribute of marine alga (Haeterosigma akashiwo).Experiment conducted with inhibitor of uncoupler 2,4-DNP (2,4-dinitropheno) revealed thatNR (nitrate reductase) activity is responsible for NO formation.