The rapidly expanding demand for sustainable and clean energy systems has inspired continuous innovation on energy storage technologies and devices. [1,2] Lithium-sulfur

Lithium-sulfur (Li-S) batteries have attracted considerable attentions in electronic energy storage and conversion because of their high theoretical energy density and cost effectiveness. The rapid capacity degradation, mainly caused by the notorious shuttle effect of polysulfides (PSs), remains a great challenge preventing practical application. Porous organic polymers (POPs) are one type of promising carbon materials to confine PSs within the cathode region. Here, the research progress on POPs and POPs-derived carbon materials in Li-S batteries is summarized, and the importance of pore surface chemistry in uniform distribution of sulfur and effective trapping of PSs is highlighted. POPs serve as promising sulfur host materials, interlayers, and separators in Li-S batteries. Their significance and innovation, especially new synthetic methods for promoting sulfur content, reversible capacity, Coulombic efficiency and cycling stability, have been demonstrated. The perspectives and critical challenges that need to be addressed for POPsbased Li-S batteries are also discussed. Some attractive electrode materials and concepts based on POPs have been proposed to improve energy density and electrochemical performance, which are anticipated to shed some light on future development of POPs in advanced Li-S batteries. a theoretical capacity of 3840 mA h g −1 , the conventional Li-S batteries could provide an average battery voltage of 2.2 V and a high theoretical energy density of 2570 W h kg −1 , which is 2-3 times higher than practical energy density of the commercial lithium ion batteries (LIBs). [4][5][6] Moreover, low cost, natural abundance, and environmental friendliness of sulfur endow Li-S batteries with great development potential and space compared with LIBs. Despite the overwhelming advantages, the practical application of Li-S batteries suffers from several technological obstacles, such as (i) poor electrical conductivities of sulfur and solid-state discharging products (Li 2 S 2 and Li 2 S); (ii) the dissolution of soluble lithium polysulfides (PSs) intermediates in the electrolytes and their free migration between cathode and anode, which results in notorious shuttle effect of PSs; (iii) huge volume fluctuation (≈80%) of the active materials during discharge and charge owing to large density difference between element sulfur and solid-state products. The major disadvantage is the shuttle effect of PSs among the above problems. During discharge and charge cycle, the dissolved high-order PSs generated in the cathode move toward the anode and react with lithium metal to form low-order PSs or a passive layer on the anode surface, low-order PSs diffuse back to the cathode and produce high-order PSs again. This process usually causes irreversible loss of active materials and low Coulombic efficiency, which are associated with fast capacity fading, low energy efficiency, severe self-discharge, and poor cycling stability. [1,[7][8][9][10] To address these problems, considerable efforts have been devoted to the devel...

Tamoxifen remains the most effective treatment for estrogen receptor α (ERα)‐positive breast cancer. However, many patients still develop resistance to tamoxifen in association with metastatic recurrence, which presents a tremendous clinical challenge. To better understand tamoxifen resistance from the perspective of the tumor microenvironment, the whole microenvironment landscape is charted by single‐cell RNA sequencing and a new cancer‐associated fibroblast (CAF) subset, CD63 + CAFs, is identified that promotes tamoxifen resistance in breast cancer. Furthermore, it is discovered that CD63 + CAFs secrete exosomes rich in miR‐22, which can bind its targets, ER α and PTEN, to confer tamoxifen resistance on breast cancer cells. Additionally, it is found that the packaging of miR‐22 into CD63 + CAF‐derived exosomes is mediated by SFRS1. Furthermore, CD63 induces STAT3 activation to maintain the phenotype and function of CD63 + CAFs. Most importantly, the pharmacological blockade of CD63 + CAFs with a CD63‐neutralizing antibody or cRGD‐miR‐22‐sponge nanoparticles enhances the therapeutic effect of tamoxifen in breast cancer. In summary, the study reveals a novel subset of CD63 + CAFs that induces tamoxifen resistance in breast cancer via exosomal miR‐22, suggesting that CD63 + CAFs may be a novel therapeutic target to enhance tamoxifen sensitivity.

Objective-Activation of liver X receptor (LXR) inhibits atherosclerosis but induces hypertriglyceridemia. In vitro, it has been shown that mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor synergizes LXR ligand-induced macrophage ABCA1 expression and cholesterol efflux. In this study, we determined whether MEK1/2 (U0126) and LXR ligand (T0901317) can have a synergistic effect on the reduction of atherosclerosis while eliminating LXR ligandinduced fatty livers and hypertriglyceridemia. We also set out to identify the cellular mechanisms of the actions. Approach and Results-Wild-type mice were used to determine the effect of U0126 on a high-fat diet or high-fat diet plus T0901317-induced transient dyslipidemia and liver injury. ApoE deficient (apoE −/− ) mice or mice with advanced lesions were used to determine the effect of the combination of T0901317 and U0126 on atherosclerosis and hypertriglyceridemia. We found that U0126 protected animals against T0901317-induced transient or long-term hepatic lipid accumulation, liver injury, and hypertriglyceridemia. Meanwhile, the combination of T0901317 and U0126 inhibited the development of atherosclerosis in a synergistic manner and reduced advanced lesions. Mechanistically, in addition to synergistic induction of macrophage ABCA1 expression, the combination of U0126 and T0901317 maintained arterial wall integrity, inhibited macrophage accumulation in aortas and formation of macrophages/foam cells, and activated reverse cholesterol transport. The inhibition of T0901317-induced lipid accumulation by the combined U0126 might be attributed to inactivation of lipogenesis and activation of lipolysis/fatty acid oxidation pathways. Conclusions-Our study suggests that the combination of mitogen-activated protein kinase kinase 1/2 inhibitor and LXR ligand can function as a novel therapy to synergistically reduce atherosclerosis while eliminating LXR-induced deleterious effects. (Arterioscler Thromb Vasc Biol. 2015;35:948-959.