Furthermore, we found CIRBP mediated cardiac ubiquinone (CoQ10 ) biosynthesis play an important role in extending heart preservation and ubiquinone biosynthesis protein COQ9 was an essential down-stream regulator during this process. Finally, we found that zr17-2, a CIRBP agonist, could enhance the expression of CIRBP, which further enhances the synthesis of CoQ10 and promotes scavenge of reactive oxygen species and ATP production to extend the heart preservation. This study demonstrated that CIRBP enhanced CoQ10 biosynthesis during hypothermic heart preservation and zr17-2 supplemented UW solution could be a promising approach to ameliorate heart damage and extend heart preservation during cardiac transport. This article is protected by copyright. All rights reserved.Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease (LSD) caused by inactivating mutations in the CLN1 gene. CLN1 encodes palmitoyl-protein thioesterase-1 (PPT1), a lysosomal enzyme that catalyzes the deacylation of S-palmitoylated proteins to facilitate their degradation and clearance by lysosomal hydrolases. Despite the discovery more than two decades ago that CLN1 mutations causing PPT1-deficiency underlies INCL, the precise molecular mechanism(s) of pathogenesis has remained elusive. Here we report that autophagy is dysregulated in Cln1-/- mice, which mimic INCL and in postmortem brain tissues as well as cultured fibroblasts from INCL patients. Moreover, Rab7, a small GTPase, critical for autophagosome-lysosome fusion, requires S-palmitoylation for trafficking to the late endosomal/lysosomal membrane where it interacts with RILP (Rab-interacting lysosomal protein), essential for autophagosome-lysosome fusion. Notably, Ppt1-deficiency in Cln1-/- mice, dysregulated Rab7-RILP interaction and preventing autophagosome-lysosome fusion, which impaired degradative functions of the autolysosome leading to INCL pathogenesis. Selleck DL-Thiorphan Importantly, treatment of Cln1-/- mice with a brain-penetrant, PPT1-mimetic, small molecule, N-tert (Butyl)hydroxylamine (NtBuHA), ameliorated this defect. Our findings reveal a previously unrecognized role of CLN1/PPT1 in autophagy and suggest that small molecules functionally mimicking Ppt1 may have therapeutic implications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.I read with great interest the systematic review by Ludvigsson on the coronavirus disease 2019 (COVID-19) (1). The author needs to be complimented for a well-timed, rigorous and rapid synthesis of the evidence from the rather scant data available on how the virus affects children. The review, which focused on all papers published up to 19 March, drew important conclusions that have significant practical implications for those involved in providing acute care for children suffering from this disease. This article is protected by copyright. All rights reserved.Women’s work has traditionally been considered less hazardous to health in comparison with men’s work. The increased women’s participation in the workforce has led to an increased attention to women’s working conditions. Women and men are unequally represented in individual professions or sectors (horizontal segregation), with women also under-represented in leadership positions (vertical segregation). The selection of specific occupations can result in differences between types and levels of occupational exposures among women and men, and can affect prevalence of occupational allergy. Gender distribution of work-related asthma appears to vary across countries without clear global difference. Occupational rhinitis tends to be higher in women, although is not clear if this is related to a sex/gender effect or to differences in work exposure. Women are more likely to have occupational contact dermatitis, mainly due to wet work. No clear effects of gender on rates of hypersensitivity pneumonitis have been shown. Besides variation in exposures, physical and physiological characteristics, different behaviors and health consciousness have an impact on the occupational health hazards of women and men. Occupational allergy health promotion strategies need to consider approaches for women and men adjusted by gender, and legislative actions similarly could be implemented in a more gender-sensitive way. This article is protected by copyright. All rights reserved.OBJECTIVE During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate to use tests with respect to irritation elicited by skin care (leave-on) products. METHODS/RESULTS A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that cat simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter. This article is protected by copyright. All rights reserved.The aim of the study was to compare expanded hemodialysis (HDx) with hemodiafiltration (HDF) at different infusion flows to identify the main determinants, namely blood flow (Qb), replacement volume, infusion flow (Qi), ultrafiltration flow (Quf ), filtration fraction (FF), and the point at which the effectiveness of HDF equals or exceeds that of HDx. We conducted a prospective, single-center study in 12 patients. Each patient underwent 12 dialysis sessions six sessions with Qb 350 and six with Qb 400 ml/min; with each Qb, one session was with HDx and five sessions were with FX80 (one in HD, and four with Qi 50, 75, 90/100 mL/min or autosubstitution in postdilution HDF). The reduction ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually and the global removal score (GRS) was calculated. The mean replacement volume with Qb 350 mL/min was 13.77 ± 0.92 L with Qi 50 mL/min, 20.75 ± 1.17 L with Qi 75, 23.83±1.