Pigment production is a unique character of melanocytes. Numerous factors are linked with melanin production, including genetics, ultraviolet radiation (UVR) and inflammation. Understanding the mechanism of melanogenesis is crucial to identify new preventive and therapeutic strategies in the treatment of melanoma. Here, we reviewed the current available literatures on the mechanisms of melanogenesis, including the signaling pathways of UVR-induced pigment production, MC1R’s central determinant roles and MITF as a master transcriptional regulator in melanogenesis. Moreover, we further highlighted the role of targeting BRAF, NRAS and MC1R in melanoma prevention and treatment. The combination therapeutics of immunotherapy and targeted kinase inhibitors are becoming the newest therapeutic option in advanced melanoma.

Most governments strive for an ecological civilization so the efficiency of government expenditure on environmental protection (EPEE) is an important issue. While it is recognized that foreign direct investment (FDI) enhances environmental protection, this investigation focuses on the effects of FDI on the efficiency of government expenditure on environmental protection under fiscal decentralization. Analysis is conducted using an output-oriented data envelopment analysis (DEA) scale return model to calculate the efficiency of environmental protection spending in China. Then, a spatial model is built to test the linkages among FDI, fiscal decentralization and the efficiency of government expenditure. The results reveal that, firstly, the efficiency of government spending has been enhanced over the last 10 years. Secondly, FDI is positively correlated with the efficiency of government environmental expenditure in terms of both quantity and quality of spending and it has a positive spillover effect. Thirdly, financial decentralization is negatively correlated with the efficiency of environmental spending, but it improves the effect of FDI. Accordingly, policy proposals are that the government should improve the supervision system for environmental spending and local governments should pursue FDI, improve the structure of FDI and use its spillover effect to enhance the efficiency of environmental expenditure.

Programmed cell death 1 ligand 1 (PD-L1) is a ligand of programmed cell death 1 (PD-1) that functions as an immune checkpoint by down-regulating immune responses. To determine whether PD-L1 is a therapy target in vitiligo treatment, Pmel-1 vitiligo mice were treated with a PD-L1 fusion protein. Treatment with this fusion protein significantly reversed/suppressed depigmentation development in adult Pmel-1 mice. Mechanistically, enrichment of regulatory T cells (Treg) in the skin was detected after PD-L1 fusion protein treatment in Pmel-1 mice. Furthermore, Tregs abundance was also increased in both the spleen and circulation of Pmel-1 mice treated with PD-L1. These data indicate that PD-L1 protein therapy inhibits the immune response and reverses depigmentation development in Pmel-1 vitiligo mice.

Background: Psoriasis is a chronic and immune-mediated inflammatory skin disease. Many studies have shown that curcumin (CUR) has strong anti-inflammatory effects and can improve psoriasis; however, its efficacy and safety have not been confirmed, and the specific mechanism remains to be elucidated.Objective: To evaluate the efficacy, safety, and possible mechanisms of CUR in the treatment of psoriasis.Methods: The Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP (China Science and Technology Journal Database) were systematically searched for clinical trials and preclinical studies on the use of CUR in psoriasis treatment. All databases were searched from inception to January 2022. The meta-analysis was performed using RevMan 5.3 software.Results: Our meta-analysis included 26 studies, comprising seven clinical randomized controlled trials and 19 preclinical studies. A meta-analysis of clinical trials showed that both CUR monotherapy and combination therapy improved Psoriasis Area and Severity Index (PASI) scores in patients compared to controls (standard mean difference [std.MD]: −0.83%; 95% confidence interval [CI]: −1.53 to 0.14; p = 0.02). In preclinical studies, CUR showed better performance in improving the phenotype of psoriatic dermatitis mice compared to controls, including total PASI score (std.MD: 6.50%; 95% CI: 10.10 to −2.90; p = 0.0004); ear thickness (p = 0.01); and the expression of inflammatory cytokines such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-17F, and IL-22 (p < 0.05). In cell studies, CUR inhibited cell proliferation (p = 0.04) and the cell cycle (p = 0.03) and downregulated the inflammatory cytokines IL-6 and IL-8 (p < 0.05).Conclusions: CUR has excellent efficacy and broad potential to treat psoriasis in multiple ways. Its use also plays a crucial role in improving the psoriasis phenotype and reducing the inflammatory microenvironment. In conclusion, our findings suggest that CUR alone or in combination with other conventional treatments can effectively treat psoriasis.

China is a large import and export economy in global terms, and the carbon dioxide emissions and carbon leakage arising from trade have great significance for China’s foreign trade and its economy. On the basis of trade data for China’s 20 industrial sectors, we first built a panel data model to test the effect of trade on carbon dioxide emissions and the presence of carbon leakage for all industrial sectors. Second, we derived a single-region input–output model for open economies based on the industrial sectors’ diversity and carbon dioxide emissions, and performed an empirical test. We estimated the net carbon intensity embodied in export, which is 0.237tCO₂/ten thousand RMB, to divide all sectors (ACSs) into high-carbon sectors (HCSs) and low-carbon sectors (LCSs). The results show that higher trade openness leads to a reduction in the intensity of CO₂ emissions and gross emissions and that there are obvious structural differences in different sectors with different carbon emission intensity. The coefficient of trade openness for LCSs is −0.073 and is statistically significant at the 1% level, so higher trade openness for LCSs leads to a reduction in the CO₂ emissions intensity. However, the coefficient for HCSs is 0.117 and is statistically significant at the 10% level, indicating that higher trade openness increases the CO₂ emissions’ intensity for HCSs. The difference is that higher trade openness in LCSs can help reduce the CO₂ emissions’ intensity without the problem of carbon leakage and with the existence of the environmental Kuznets curve (EKC), whereas there is no EKC for HCSs and carbon leakage may happen. We introduced dummy variables and found that a “pollution haven” effect exists in HCSs. The test results in HCSs and LCSs are exactly the opposite of each other, which shows that the carbon leakage of ACSs cannot be determined. The message that can be drawn for policy makers is that China does not need to worry about the adverse impact on the environment of trade opening up and should, in fact, increase the opening up of trade, while becoming acclimatized to environmental regulation of a new trade mode and new standards. This will help amplify the favorable impact of trade opening up on the environment and improve China’s international reputation. The policies related to trade should encourage structural adjustment between the sectors via the formulation of differential policies and impose a restraint on sectors that have high levels of CO₂ emissions embodied in export.

Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitive will provide a significant improvement in patient outcome. Here we identify Mi-2β as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Studies in genetically engineered mouse melanoma models indicate that loss of Mi-2β rescues the immune response to immunotherapy in vivo. Mechanistically, ATAC-seq analysis shows that Mi-2β controls the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β binds to EZH2 and promotes K510 methylation of EZH2, subsequently activating the trimethylation of H3K27 to inhibit the transcription of ISGs. Finally, we develop an Mi-2β-targeted inhibitor, Z36-MP5, which reduces Mi-2β ATPase activity and reactivates ISG transcription. Consequently, Z36-MP5 induces a response to immune checkpoint inhibitors in otherwise resistant melanoma models. Our work provides a potential therapeutic strategy to convert immunotherapy resistant melanomas to sensitive ones.