Charge-separated states with a lifetime scale of seconds or longer not only favor studies using various steady-state analysis techniques but are important for light-energy conversion and other applications. Through a steric-hindrance-induced method, unprecedented photoinduced generation of a partially charge separated (PCS) state with a lifetime of days has been detected in the "visual" mode during the decay of excited states to a commonly observed fully charge separated (FCS) state for viologen analogues. One pale yellow 4,4′bipyridine-based metalloviologen compound, with an interannular dihedral angle of 1.84°in 4,4′-bipyridine, directly decays to the purple FCS state after photoexcitation. The other pale yellow compound, with a similar coordination framework but a larger interannular dihedral angle (33.74°), changes first to a yellow PCS state and then relaxes slowly (in the dark in Ar, ca. 2 days; 70 °C in Ar, ca. 1 h) to the purple FCS state. The two-step coloration phenomenon is unprecedented for viologen compounds and their analogues and also rather rare for other photochromic species. EPR and Raman data reveal that photoinduced charge separation first generates univalent zinc and radicals and then the received electron in Zn(I) slowly distributes further to 4,4′-bipyridine. Reduction of πconjugation and a direct to indirect change in band gap account for the prolongation of the relaxation process and the capture of the PCS state. These findings help to understand and control decay processes of excited states and provide a potential design strategy for multicolor photochromism, light-energy conversion with high efficiency, or other applications.

MicroRNAs (miRNAs) are small non-coding RNA molecules, which function in RNA silencing and post-transcriptional regulation of gene expression. Psoriasis is an inflammatory skin disease characterized by the dysfunction of keratinocytes, with the immune dysregulation. We reviewed the recent studies on the roles of miRNAs in psoriasis and showed that miRNAs play key roles in psoriasis, including the regulation of hyperproliferation, cytokine and chemokine production in keratinocyte, as well as mediating immune dysfunction in psoriasis. Furthermore, miRNAs, particularly, circulating miRNAs may serve as novel biomarkers for diagnosis, monitoring therapy response and reflecting the disease severity. Thus, targeting specific miRNAs may be used to develop new therapeutic methods for psoriasis.

Breast cancer is a heterogeneous disease with increasing incidence and mortality and represents one of the most common cancer types worldwide. Low-density lipoprotein (LDL) is a complex particle composed of several proteins and lipids, which carries cholesterol into peripheral tissues and also affects the metabolism of fatty acids. Recent reports have indicated an emerging role of LDL in breast cancer, affecting cell proliferation and migration, thereby facilitating disease progression. However, controversy still exists among distinct types of breast cancer that can be affected by LDL. Classical therapeutic approaches, such as radiotherapy, chemotherapy, and lipid-lowering drugs were also reported as affecting LDL metabolism and content in breast cancer patients. Therefore, in this review we summarized and discussed the role of LDL in the development and treatment of breast cancer.

All-trans retinoic acid (atRA), the main biologically active metabolite of vitamin A, has been implicated in immunoregulation and anti-cancer. A recent finding that vitamin A could decrease the risk of melanoma in humans indicates the beneficial role of atRA in melanoma. However, it remains unknown whether topical application of atRA could inhibit melanoma growth by influencing tumour immunity. We demonstrate topical application of tretinoin ointment (atRA as the active ingredient) effectively inhibited B16F10 melanoma growth. This is accompanied by markedly enhanced CD8 T-cell responses, as evidenced by significantly increased proportions of effector CD8 T cells expressing granzyme B, tumour necrosis factor-α, or interferon-γ, and Ki67 proliferating CD8 T cells in atRA-treated tumours compared with vaseline controls. Furthermore, topical atRA treatment promoted the differentiation of effector CD8 T cells in draining lymph nodes (DLN) of tumour-bearing mice. Interestingly, atRA did not affect tumoral CD4 T-cell response, and even inhibited the differentiation of interferon-γ-expressing T helper type 1 cells in DLN. Importantly, we demonstrated that the tumour-inhibitory effect of atRA was partly dependent on CD8 T cells, as CD8 T-cell depletion restored tumour volumes in atRA-treated mice, which, however, was still significantly smaller than those in vaseline-treated mice. Finally, we demonstrated that atRA up-regulated MHCI expression in B16F10 cells, and DLN cells from tumour-bearing mice had a significantly higher killing rate when culturing with atRA-treated B16F10 cells. Hence, our study demonstrates that topical atRA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD8 T cells.

Atherosclerosis is a leading cause of disability and death worldwide. Research into the disease has led to many compelling hypotheses regarding the pathophysiology of atherosclerotic lesion formation and the resulting complications such as myocardial infarction and stroke. Herbal medicine has been widely used in China as well as other Asian countries for the treatment of cardiovascular diseases for hundreds of years; however, the mechanisms of action of Chinese herbal medicine in the prevention and treatment of atherosclerosis have not been well studied. In this review, we briefly describe the mechanisms of atherogenesis and then summarize the research that has been performed in recent years regarding the effectiveness and mechanisms of antiatherogenic Chinese herbal compounds in an attempt to build a bridge between traditional Chinese medicine and cellular and molecular cardiovascular medicine.

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As human phosphodiesterase (PDE) proteins are attractive drug targets, a large number of selective PDE inhibitors have been developed. However, since the catalytic sites of PDE isoforms are conserved in sequence and structure, it remains unclear how these inhibitors discriminate PDE isoforms in a selective manner. Here we perform long-time scale molecular dynamics (MD) simulations to investigate the spontaneous association processes of a highly selective PDE2A inhibitor (BAY60–7550) with the catalytic pockets of six PDE isoforms. We found that the free-energy landscapes of PDE:BAY60–7550 interactions on the PDE surfaces are very different between various PDE isoforms; and the free-energy landscape of PDE2A forms a favorable low-energy pathway that not only drives BAY60–7550 toward the target binding site, but also guides BAY60–7750 to adopt its native binding conformation known from crystal structure. Thus, this study reveals that the inhibitor interactions with the PDE surface residues play an important role in its high selectivity for PDE2A, and thereby provides new fundamental insights into the PDE isoform-specific inhibitor selectivity.

Herein, we report the first redox-neutral and transition-metal-free β-C(sp 3 )−H functionalization of cyclic amines via a consecutive intermolecular hydride transfer process. A series of N-aryl pyrrolidines and N-aryl 1,2,3,4tetrahydropyridines decorated with CF 3 and carboxylic ester functionalities are directly accessed in good yields from pyrrolidines and piperidines. This work pushes forward the application of the intermolecular hydride transfer strategy in one-step assembly of molecular complexity.