Sequential Quality-Control Checkpoints Triage Misfolded Cystic Fibrosis Transmembrane Conductance Regulator

Cystic fibrosis arises from the misfolding and premature degradation of CFTR Delta F508, a Cl- ion channel with a single amino acid deletion. Yet, the quality-control machinery that selects CFTR Delta F508 for degradation and the mechanism for its misfolding are not well defined. We identified an ER membrane-associated ubiquitin ligase complex containing the E3 RMA1, the E2 Ubc6e, and Derlin-1 that cooperates with the cytosolic Hsc70/CHIP E3 complex to triage CFTR and CFTR Delta F508. Derlin-1 serves to retain CFTR in the ER membrane and interacts with RMA1 and Ubc6e to promote CFTR's proteasomal degradation. RMA1 is capable of recognizing folding defects in CFTR Delta F508 coincident with translation, whereas the CHIP E3 appears to act posttranslationally. A folding defect in CFTR Delta F508 detected by RMA1 involves the inability of CFTR's second membrane-spanning domain to productively interact with amino-terminal domains. Thus, the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508

Ascribed or achieved? : the role of birth order on innovative behaviour in the workplace

The pathway through which birth order triggers status competition and affects individuals’ subsequent innovative behaviours in the Chinese workplace remains an unexplored topic. To fill this lacuna, this study collected data from China to test the relationships. Findings showed that the first-born siblings tended to have a rational status striving orientation, which mediated the relationship between birth order and exploitative innovative behaviour; later-born siblings, though, were more likely to have an emotional status striving orientation, which weakened the relationship between birth order and exploratory innovative behaviour. Considering that expectations for the future career may affect an individual’s current decision, we also examined the moderating role of relative time distance and found that it strengthened the relationship between status striving orientation and employees’ innovative behaviour. Our study is of practical and theoretical significance by exploring the pathway through which birth order affects employees’ innovative behaviour in the Chinese context

Comparison of chicoric acid, and its metabolites caffeic acid and caftaric acid: In vitro protection of biological macromolecules and inflammatory responses in BV2 microglial cells

Chicoric acid (CA), a natural phenolic acid, has been used as a nutraceutical food ingredient due to its powerful antioxidant, anti-HIV and anti-diabetic bioactivities. CA could be partly metabolized into caffeic acid (CFA) and caftaric acid (CTA) on cytochrome P450s in rat liver microsomes. To compare the protective effects of CA and its metabolites on biomolecules and inflammatory responses, oxidative damage induced by free radicals in vitro and microglial inflammation triggered by lipopolysaccharide in BV2 cells were constructed. Results showed that CA, CTA and CFA all significantly inhibited protein degradation and carbonylation induced by hydroxyl radicals and alcoxyl radicals, and suppressed hemin/nitrite/H2O2 triggered-nitration. Moreover, CA, CTA and CFA all exerted remarkable inhibition capacities on linoleic acid and soybean lecithin liposomes peroxidation in a dose-dependent manner, and restrained the oxidation of herring sperm DNA, as well as the breakage of pBR322 plasmid DNA. Furthermore, CA and its metabolites suppressed lipopolysaccharide-induced decline of BV2 cell viability and the production of NO and ROS. However, bioactivities of CA were significantly stronger than those of its metabolites within a certain concentration range. This study provides scientific basis for the application of CA and its metabolites as nutrition and natural antioxidants

Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells

Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical characteristics including particle size, zeta potential, encapsulation efficiency, and delayed release time. Meanwhile, the targeting activity of the RGD-modified liposomes was demonstrated by flow cytometry and confocal microscopy in the αvβ3-positive MDA-MB-231 cells. Besides exhibiting greater cytotoxicity in vitro, compared with non-targeted shikonin-loaded liposomes (SSLs-SHK), RGD-SSLs-SHK could also evidently induce apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. It could also inhibit cell proliferation, migration, invasion, and adhesion by reducing the expression of MMP-9 and the level of NF-κB p65, but did not affect the expression of MMP-2 in the MDA-MB-231 cells. Therefore, these findings indicated that the strategy to use RGD-modified liposomes as carriers for targeted delivery of shikonin is a very promising approach to achieve breast cancer targeted therapy

Superhydrophilic Wrinkle-Free Cotton Fabrics via Plasma and Nanofluid Treatment

We demonstrate in this study a wrinkle-free, superhydrophilic cotton fabric (contact angle ∼0°) by uniformly attaching specially engineered nanoparticles to plasma-pretreated cotton fabric. Because of their highly charged nature, the nanoparticles are firmly anchored on the fabric via electrostatic interactions, as confirmed by microscopy and chemical analyses. The durability of wetting behavior and wrinkle-free property of the nanoparticle-coated fabrics were evaluated via aging, laundering, and abrasion tests. The strongly attached coatings are stable enough to maintain their superhydrophilic nature even after 60 days of aging at room temperature, 50 laundering cycles, and 25 000 abrasion cycles. Moreover, the nanoparticle-coated superhydrophilic fabrics exhibit great wrinkle-recovery property, tensile strength, and abrasion resistance performance up to 25 000 abrasion cycles

Effects of Long-Term Guo Lin Qi-Gong Practice on Cancer Survivors\u27 Quality of Life and Aerobic Capacity: A Preliminary Report

While the positive impact of aerobic and strength exercises on quality of life (QOL) and physical functions among cancer survivors has been well documented, limited efforts have been made to examine the effects of body-mind exercises. PURPOSE: To determine the effects of long-term Guo Lin Qi-gong practice on QOL and aerobic capacity in cancer survivors. Guo Lin Qi-gong is a body-mind exercise that has been practiced by thousands of cancer survivors in China. METHOD: 40 (20 males/females) Chinese long-term cancer survivors, who have practiced Guo Lin Qi-gong since their cancer diagnosis, were recruited in Shanghai, China and a control group (n=40) matched by types of cancer, age, gender and survival years was then recruited. Both groups were administered SF-36, a generic QOL measure (Ware & Donald-Sherbourne, 1992), Beck Depression Inventory (Beck, 1961), and did a 6-min walking test, and all results were compared using paired t-tests. RESULTS: Both groups were well matched by Age in yr., HT in cm, WT in kg, DXA Fat% & Survival yr. (M±SD): Guo Lin Qi-gong (61.98±7.31, 163.92±6.19, 63.04±9.82, 28.30±9.36, 16.54±4.12) vs. Match-Control (60.98±7.75, 164.40±7.49, 64.14±10.95, 29.31±8.37, 15.67±4.61). It was found that long term Guo-Lin Qi-gong practice led to: 1. Better health status and QOL [e.g., Guo Lin Qi-gong group\u27s SF-36 and related subscale scores are all higher than the Control group, and the difference in body pain scores, 91.35±11.33 vs. 84.60±15.61 (note: the higher SF-36 score, the better health) is statistically significant, p \u3c.05]; 2. Less depression (e.g., Guo Lin Qi-gong group 7.55±3.78 vs. Control group 8.91±6.64) although the difference was not statistically different (p \u3e.05); 3. Higher health fitness level (e.g., Guo Lin Qi-gong group walked longer distances, 566.65±70.63 vs. 542.68±85.19 meters, and took more steps, 837.75±81.05 vs. 775.95±71.56 steps, p \u3c.05, in 6-min walking test than the Control group). Furthermore, it was found that Guo Lin Qi-gong group experienced a much lower cancer recurrence rate (4/40 = 10%) than the Control group (12/40 = 30%). CONCLUSION: Guo Lin Qi-gong demonstrated to be an effective means in improving QOL and aerobic capacity for cancer survivors. Its possible effect in preventing cancer recurrence should be further investigated