Power train electrification is promoted as a potential alternative to reduce carbon intensity of transportation. Lithium-ion batteries are found to be suitable for hybrid electric vehicles (HEVs) and pure electric vehicles (EVs), and temperature control on lithium batteries is vital for long-term performance and durability. Unfortunately, battery thermal management (BTM) has not been paid close attention partly due to poor understanding of battery thermal behaviour. Cell performance change dramatically with temperature, but it improves with temperature if a suitable operating temperature window is sustained. This paper provides a review on two aspects that are battery thermal model development and thermal management strategies. Thermal effects of lithium-ion batteries in terms of thermal runaway and response under cold temperatures will be studied, and heat generation methods are discussed with aim of performing accurate battery thermal analysis. In addition, current BTM strategies utilised by automotive suppliers will be reviewed to identify the imposing challenges and critical gaps between research and practice. Optimising existing BTMs and exploring new technologies to mitigate battery thermal impacts are required, and efforts in prioritising BTM should be made to improve the temperature uniformity across the battery pack, prolong battery lifespan, and enhance the safety of large packs.

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N6-methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3′UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress-induced cellular senescence. Our findings on p21 mRNA methylation and expression reveal that joint m6A and m5C modification of the same RNA may influence each other, coordinately affecting protein expression patterns.

The methyltransferase like 3 (METTL3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNAs including mRNA, tRNA, rRNA, small nuclear RNA, microRNA precursor and long non-coding RNA. However, the characteristics of METTL3 in activation and post-translational modification (PTM) is seldom understood. Here we find that METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1. SUMOylation of METTL3 does not alter its stability, localization and interaction with METTL14 and WTAP, but significantly represses its m6A methytransferase activity resulting in the decrease of m6A levels in mRNAs. Consistently with this, the abundance of m6A in mRNAs is increased with re-expression of the mutant METTL3-4KR compared to that of wild-type METTL3 in human non-small cell lung carcinoma (NSCLC) cell line H1299-shMETTL3, in which endogenous METTL3 was knockdown. The alternation of m6A in mRNAs and subsequently change of gene expression profiles, which are mediated by SUMOylation of METTL3, may directly influence the soft-agar colony formation and xenografted tumor growth of H1299 cells. Our results uncover an important mechanism for SUMOylation of METTL3 regulating its m6A RNA methyltransferase activity.

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NCT01770431; Post-results.

Mesenchymal stem/stromal cells (MSCs) have great clinical potential in modulating inflammation and promoting tissue repair. Human embryonic stem cells (hESCs) have recently emerged as a potentially superior cell source for MSCs. However, the generation methods reported so far vary greatly in quality and efficiency. Here, we describe a novel method to rapidly and efficiently produce MSCs from hESCs via a trophoblast-like intermediate stage in approximately 11-16 days. We term these cells "T-MSCs" and show that T-MSCs express a phenotype and differentiation potential minimally required to define MSCs. T-MSCs exhibit potent immunomodulatory activity in vitro as they can remarkably inhibit proliferation of cocultured T and B lymphocytes. Unlike bone marrow MSCs, T-MSCs do not have increased expression of inflammatory mediators in response to IFNc. Moreover, T-MSCs constitutively express a high level of the immune inhibitory ligand PD-L1 and elicit strong and durable efficacy in two distinct animal models of autoimmune disease, dextran sulfate sodium induced colitis, and experimental autoimmune encephalomyelitis, at doses near those approved for clinical trials. Together, we present a simple and fast derivation method to generate MSCs from hESCs, which possess potent immunomodulatory properties in vitro and in vivo and may serve as a novel and ideal candidate for MSC-based therapies. STEM CELLS 2016;34:380-391 SIGNIFICANCE STATEMENTHere, we report a novel method to derive MSCs from hESCs via a trophoblast intermediate stage called T-MSCs. This method is the most rapid and simple method to derive hESC-MSCs reported to date. T-MSCs elicit strong and durable efficacy in two distinct animal models of autoimmune disease at lower doses approaching those approved for clinical trials. Our findings suggest that T-MS, which can be reliably derived from an unlimited source of hESCs, can be developed into a novel therapy for autoimmune diseases with stronger efficacy and higher safety than MSCs derived from adult tissues.