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A sulfur-linked carbonyl-based poly(2,5-dihydroxyl-1,4-benzoquinonyl sulfide) (PDHBQS) compound is synthesized and used as cathode material for lithium-ion batteries (LIBs). Flexible binder-free composite cathode with single-wall carbon nanotubes (PDHBQS-SWCNTs) is then fabricated through vacuum filtration method with SWCNTs. Electrochemical measurements show that PDHBQS-SWCNTs cathode can deliver a discharge capacity of 182 mA h g (0.9 mA h cm ) at a current rate of 50 mA g and a potential window of 1.5 V-3.5 V. The cathode delivers a capacity of 75 mA h g (0.47 mA h cm ) at 5000 mA g , which confirms its good rate performance at high current density. PDHBQS-SWCNTs flexible cathode retains 89% of its initial capacity at 250 mA g after 500 charge-discharge cycles. Furthermore, large-area (28 cm ) flexible batteries based on PDHBQS-SWCNTs cathode and lithium foils anode are also assembled. The flexible battery shows good electrochemical activities with continuous bending, which retains 88% of its initial discharge capacity after 2000 bending cycles. The significant capacity, high rate performance, superior cyclic performance, and good flexibility make this material a promising candidate for a future application of flexible LIBs.

Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed and approved by Food and Drug Administration for the treatment of non-small-cell lung cancers, but their efficacy can be compromised by acquired drug resistance conferred by EGFR-mutant variants. Here, we described the discovery of a novel E3 ligase von Hippel-Lindau-recruiting EGFR degrader, MS39 (compound 6), and a first-in-class E3 ligase cereblon-recruiting EGFR degrader, MS154 (compound 10), using the proteolysis targeting chimera technology. These compounds potently induced the degradation of mutant but not wild-type EGFR in an E3 ligasedependent manner in cancer cell lines and effectively suppressed the growth of lung cancer cells

The immune-response gene 1 (IRG1) plays a key role in anti-pathogen defense, as deletion of Irg1 in mice causes severe defects in response to bacterial and viral infection, and decreased survival 1, 2 . IRG1 transcription is rapidly induced by pathogen infection and in ammatory conditions primarily in cells of myeloid lineage 3 . IRG1 encodes a mitochondrial metabolic enzyme, aconitate decarboxylase 1 (ACOD1), that catalyzes the decarboxylation of cis-aconitate to produce the anti-in ammatory metabolite itaconic acid (ITA) 4 . Several molecular processes are affected by ITA, including succinate dehydrogenase (SDH) inhibition 5 , resulting in succinate accumulation and metabolic reprogramming 6,7 , and alkylation of protein cysteine residues, inducing the electrophilic stress response mediated by NRF2 and IκBζ 8, 9 and impairing aerobic glycolysis 10 . However, the mechanisms by which ITA exerts its profound antiin ammatory effect still remains to be fully elucidated. Here, we show that ITA is a potent inhibitor of the TET family DNA dioxygenases, which catalyze the conversion of 5-methylcytosine (5mC) to 5hydroxymethylcytosine (5hmC) during the process of active DNA demethylation. ITA binds to the same site of α-ketoglutarate (α-KG) in TET2, inhibiting its catalytic activity. Lipopolysaccharides (LPS) treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals TET2 is a major target of ITA in suppressing LPS-induced genes, including those regulated by NF-κB and STAT signaling pathways. In vivo, ITA decreases 5hmC, reduces LPS-induced acute pulmonary edema and lung and liver injury, and protects mice against lethal endotoxaemia in a manner that is dependent on the catalytic activity of Tet2. Our study thus identi es ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the in ammatory response. MainDeletion of the Irg1 gene or treatment with cell permeable ITA alters the transcriptional signature in response to LPS 2 . We speculated that ITA may impact epigenetics to in uence gene expression, and therefore, we determined the effect of Irg1 expression and ITA accumulation on global histone and DNA de/methylation in transfected HEK293T cells (Extended Data Fig. 1a). We found that ectopic expression of either wild-type or catalytic inactive mutant Irg1 had little effect on mono-, di-, and trimethylation of all ve histone H3 lysine residues (Extended Data Fig. 1b, 1c). In contrast, expression of wild-type Irg1, but not the catalytic inactive mutant, dramatically reduced Tet2-mediated global 5hmC in cells (Fig. 1a and Extended Data Fig. 1d-e). Like α-KG, which is a crucial co-substrate for the activity of TET2, ITA is also a dicarboxylic acid containing a 4-or 5-carboxylate that, in the case of α-KG, forms hydrogen and ionic bonds with H1416, R1896, and S1898 in TET2 11 . Of note, α-KG binds to Fe(II) in a bidentate manner via its C-1 carboxylate and C-2 keto groups, which are lacking in ITA. This raises the possibi...