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Lithium‐ion batteries (LIBs) have become the main choice for electric vehicles (EVs). However, the thermal runaway problems of LIBs largely limit the wider promotion of EVs. To provide background and insight for the improvement of battery safety, the general working mechanism of LIBs is described in this review, followed by a discussion of the thermal runaway process, including the trigger conditions and material factors. Moreover, advances made to improve battery safety are examined from the perspective of battery materials and management systems. Thus, this review provides a general picture of the thermal runaway risks of LIBs and corresponding solutions with the aim of facilitating safer battery designs.

Gas diffusion layers (GDLs) are the most rigid layers in a 5‐layer or 7‐layer membrane electrode assembly (MEA) of a proton exchange membrane fuel cell. Therefore, in the fuel cell analysis, the mechanical properties of GDLs have a great impact on the stress distribution of the membrane as well as the performance of the whole cell. However, the mechanical properties of GDLs are not sufficiently studied. Nonlinear behavior of GDLs under cyclic compression is discussed rarely in literature. The existing model takes both constraints into consideration, but due to a geometrical oversimplification of the carbon paper microstructure, it shows some deviation, which cannot be overcome by selecting appropriate parameters. In this paper, the geometry of carbon paper microstructure has been reanalyzed. Based on the improved geometry formula, a modified model of carbon paper GDL is presented and verified by experimental data. Furthermore, both the experimental mechanical characteristics are achieved as support data for the improved model.

Heat shock protein 90 (HSP90) binds and stabilizes numerous proteins and kinases essential for myeloma cell survival and proliferation. We and others have recently demonstrated that inhibition of HSP90 by small molecular mass inhibitors induces cell death in multiple myeloma (MM). However, some of the HSP90 inhibitors involved in early clinical trials have shown limited antitumor activity and unfavorable toxicity profiles. Here, we analyzed the effects of the novel, orally bioavailable HSP90 inhibitor NVP-HSP990 on MM cell proliferation and survival. The inhibitor led to a significant reduction in myeloma cell viability and induced G2 cell cycle arrest, degradation of caspase-8 and caspase-3, and induction of apoptosis. Inhibition of the HSP90 ATPase activity was accompanied by the degradation of MM phospho-Akt and phospho-ERK1/2 and upregulation of Hsp70. Exposure of MM cells to a combination of NVP-HSP990 and either melphalan or histone deacetylase (HDAC) inhibitors caused synergistic inhibition of viability, increased induction of apoptosis, and was able to overcome the primary resistance of the cell line RPMI-8226 to HSP90 inhibition. Combined incubation with melphalan and NVP-HSP990 led to synergistically increased cleavage of caspase-2, caspase-9, and caspase-3. These data demonstrate promising activity for NVP-HSP990 as single agent or combination treatment in MM and provide a rationale for clinical trials.

CVT-510 (N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside), a selective A 1 adenosine receptor (AdoR) agonist, is being developed as an AV nodal blocking agent for acute control of ventricular rate during atrial fibrillation and flutter and management of AV nodal reentrant tachycardias. A 1 AdoR agonists are also known to cause sinus bradycardia. In the present study, we characterized the bradycardic effect of CVT-510 in anesthetized and awake rats. In anesthetized rats, intravenous infusions of CVT-510 slowed heart rate in a dose-dependent manner. At doses of 0.5-1.0 μg/kg (1.5-3.0 nmol/kg) and >1.5 μg/ kg (4.5 nmol/kg), CVT-510 slowed heart rate by 30-40% and >50% of baseline, respectively. The sinus bradycardia caused by CVT-510 was reversible upon termination of infusion. The decreases in heart rate caused by CVT-510 were accompanied by stepwise increases in plasma levels of CVT-510. The relationship between plasma levels of CVT-510 and slowing of heart rate yielded a correlation coefficient (R value) of 0.9. In awake rats CVT-510 given by repeated (n = 7) intraperitoneal (ip) injections or by chronic (4 days) subcutaneous (sc) administration caused reproducible, dose-dependent, and persistent bradycardia. Injections ip of 50 μg/kg (148 nmol/kg) CVT-510 caused sinus bradycardias of > 100 bpm. Continuous sc administration of CVT-510 (e.g., 100 nmol/kg/h) slowed heart rate by 80-60 bpm throughout the duration of infusion, i.e., 4 days. Thus, in rats the sinus bradycardia caused by CVT-510 does not undergo desensitization due to repeated injections and is persistent, with minimal attenuation during chronic administration.

The four human adenosine receptors (ARs), A 1 , A 2A , A 2B , and A 3 , have been stably expressed in mammalian cells. Radioligand binding properties were examined for all four subtypes, including, for the first time the A 2B AR. The A 1 AR-selective radioligand, [ 3 H]8-cyclopentyl-1,3-dipropylxanthine ([ 3 H]CPX; A 1 ; K D = 2 nM) also can be used to characterize recombinant A 2B AR (K D = 40 nM). Theophylline and enprofylline both bind to A 2B AR with K 1 of 7 μM, well within the therapeutic ranges of these compounds used to treat asthma. We have identified C B -(N-methylisopropyl)-amino-N 6 -(5'-endohydroxy)-endonorbornan-2-yl-9-methyladenine (WRC-0571) as the most selective antagonist of A 1 AR. Recombinant ARs have been extended with hexahistidine (H) and the FLAG (F) epitope to make H/F-A 1 and H/F-A 2A receptors that have been purified to near homogeneity under conditions that preserve radioligand binding. [ 3 H]Adenosine binds to purified H/F-A 1 AR-G protein complexes with a Ko of 0.95 ± 0.3 nM; binding is not affected by the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA). Phosphoaminoacid analysis of H/F-A 1 AR and H/F-A 2A AR purified from mammalian cells incubated in [ 32 P]phosphate indicates that both receptors are phosphorylated on serine residues. Monoclonal antibodies were raised by using the purified H/F-A 2A AR as an antigen. Antibodies with higher affinity than antipeptide antisera were generated and used for Western blotting and rat brain immunocytochemistry.

Compound 20 (CVT-3146--a 2-[(N-1-(4-N-methylcarboxamidopyrazolyl)] adenosine derivative) and compound 31 (CVT-3033--a 2-[(4-(1-N-pentylpyrazolyl)] adenosine derivative), were found to be short acting functionally selective coronary vasodilators (CV t0.5 = 5.2 +/- 0.2 and 3.4 +/- 0.5 min, respectively--rat isolated heart 50% reversal time) with good potency (EC50S = 6.4 +/- 1.2 nM and 67.9 +/- 16.7 nM, respectively), but they possess low affinity for the ADO A2A receptor (Ki = 1122 +/- 323 nM and 2138 +/- 952 nM, respectively; pig striatum).