Life makes cities greener: The impact of dual-policy of China in urban transformation on residents' green lifestyles.

Promoting the formation of the green lifestyle (GL) is a crucial step in achieving comprehensive green transformation of urban economic and social development. The widespread adoption of GL is influenced by various environmental regulations. Previous research mainly focused on the impact of individual policies on GL from the single policy perspective. The mechanisms of the combined effects of policies have not been thoroughly explored, particularly the contributions of each policy during periods of overlap. This paper takes the dual-policy of the New-type Urbanization Policy (NUP) and Smart City Policy (SCP) in China as an example. It employs panel data collected from 271 cities in China during 2007-2019 and establishes a multi-period difference-in-difference model to identify the combined effects of the dual-policy on residents' GL. Additionally, the Shapley value decomposition method is utilized to identify the contribution magnitude of each policy when they act simultaneously. The following conclusions are yielded. Firstly, the combined effects of dual-policy are more effective than a single policy in influencing residents' GL. Secondly, the Shapley value decomposition method reveals that when both policies are simultaneously implemented, SCP contributes a greater weight compared to NUP. Thirdly, the dual-policy can promote residents' adoption of GL through mechanisms such as green technological innovation, public participation in environmental protection, and the agglomeration of tertiary industries. Fourthly, the impact of dual-policy on residents' GL varies across different types and sizes of cities. This study attempts to unseal the "black box" of how the dual-policy influences residents' GL during the green transformation of cities in China, providing theoretical references for relevant urban policies in other countries and contributing to Chinese solutions and experience to global urban green development.

Clioquinol rescues yeast cells from Aß42 toxicity via the inhibition of oxidative damage.

Alzheimer's disease (AD), the most common form of dementia, has gotten considerable attention. Previous studies have demonstrated that clioquinol (CQ) as a metal chelator is a potential drug for the treatment of AD. However, the mode of action of CQ in AD is still unclear. In our study, the antioxidant effects of CQ on yeast cells expressing Aß42 were investigated. We found that CQ could reduce Aß42 toxicity by alleviating reactive oxygen species (ROS) generation and lipid peroxidation level in yeast cells. These alterations were mainly attributable to the increased reduced glutathione (GSH) content and independent of activities of superoxide dismutase (SOD) and/or catalase (CAT). CQ could affect antioxidant enzyme activity by altering the transcription level of related genes. Interestingly, it was noted for the first time that CQ could combine with antioxidant enzymes to reduce their enzymatic activities by molecular docking and circular dichroism spectroscopy. In addition, CQ restored Aß42-mediated disruption of GSH homeostasis via regulating YAP1 expression to protect cells against oxidative stress. Our findings not only improve the current understanding of the mechanism of CQ as a potential drug for AD treatment but also provide ideas for subsequent drug research and development.

Antiproliferative and apoptotic activity of gemcitabine-lauric acid conjugate on human bladder cancer cells.

Objectives: Gemcitabine is a first-line drug for the treatment of bladder cancer. One of the most important mechanisms of gemcitabine resistance is the low expression of cellular membrane transporter hENT1. Various derivatives containing fatty acid side chains have been developed in order to facilitate gemcitabine uptake and prolong its retention in cells, such as CP-4126. In this study, the anti-tumor effect and mechanism of a new derivative of gemcitabine named SZY-200 on bladder cancer cells were investigated. SZY-200 was assembled from the gemcitabine-lauric acid conjugate. Materials and Methods: Antiproliferative activities of SZY-200 and lauric acid were evaluated using CCK-8 assay and clonogenic survival assay. The hENT1 inhibitor NBMPR was employed to determine the role of hENT1 in the apoptotic activity of GEM, CP-4126, and SZY-200. RT-qPCR, flow cytometry, fluorescence microscope, western blotting, and wound healing assay were used to study the mechanisms of SZY-200. The target genes were predicted using the BATMAN-TCM database. Results: Our data showed that SZY-200 could inhibit the proliferation of bladder cancer cells by inducing cell cycle arrest and apoptosis. The inhibitory effects were comparable to gemcitabine and CP-4126. SZY-200 does not rely on hENT1 to help it enter bladder cancer cells. Also, we found that lauric acid could inhibit the proliferation of bladder cancer cells. SZY-200 could down-regulate the expressions of PPARG and PTGS2 which were related to the occurrence and development of bladder cancer. Conclusion: SZY-200 has the same or more advantages as CP-4126 and could be an ideal candidate drug for further in vivo investigation.

Aspirin damages the cell wall of Saccharomyces cerevisiae by inhibiting the expression and activity of dolichol-phosphate mannose synthase 1.

Aspirin is a commonly used anti-inflammatory, analgesic and antithrombotic drug. It has attracted attention due to its potential antifungal therapeutic effect; however, the molecular mechanism is poorly understood. Here, the effects of aspirin on the cell wall of Saccharomyces cerevisiae were explored. We observed by scanning electron microscopy that aspirin could damage the cell wall ultrastructure. Meanwhile, a cellular surface hydrophobicity (CSH) assay showed that aspirin increased the hydrophobicity of the yeast cell surface. A drug sensitivity assay indicated that the overexpression of dolichol phosphate mannose synthase 1 (DPM1) reversed the cell wall damage and decreased the CSH induced by aspirin. Importantly, aspirin decreased the expression and enzyme activity of DPM1 in S. cerevisiae. Molecular docking results demonstrated that aspirin could directly bind to the Ser141 site of DPM1. Similarly, we found that aspirin damaged the cell wall and inhibited the expression of DPM1 in Candida albicans. These findings improve the current understanding of the action mode of aspirin and provide new strategies for antifungal drug design.

How does the ecological compensation mechanism adjust the industrial structure? Evidence from China.

The ecological compensation (EC) mechanism is an innovative institutional arrangement which can effectively realize the coordinated development of social-economic growth and ecological protection. The current research on the evaluation of the implementation effect of EC mechanism mainly focuses on its environmental performance, how the EC mechanism guides the economically underdeveloped areas in the upper reaches of the basin to embark on the road of high-quality economic development, especially the mechanism of how EC triggers the optimization and upgrading of industrial structure, it is a topic worthy of in-depth discussion. This study takes China's first cross-provincial horizontal EC mechanism pilot (Xin'an River Basin EC) as the research object and regards it as a quasi-natural experiment. This paper selects the annual panel data of the 11 cities involved from 2009 to 2019 and builds a DID model to study the mechanism of EC affecting industrial structure adjustment systematically. The results show that the EC mechanism mainly promotes the adjustment of the industrial structure in the pilot area through two paths, this is achieved by triggering the transfer of backward or highly polluting industries and promoting the upgrading of the industrial structure. At the same time, technological innovation plays a part intermediary role in the impact of EC to promote the upgrading of industrial structure. Further analysis found that the larger the funds of compensation input, the higher the assessment intensity, the better the effects are. Finally, this study puts forward relevant policy recommendations to further release the potential of the horizontal EC for the reference of decision-makers.

Does the EU emissions trading system help reduce PM2.5 damage? A research based on PSM-DID method.

Air quality issues, especially haze pollution, have become an important aspect that threatens the sustainable development and health of human beings. Previous studies on the environmental effects of emissions trading system (ETS) mainly focused on carbon emission reduction, instead of focusing on the synergistic governance effect between carbon emission and PM2.5 reduction. Based on the PSM-DID method and the World Development Index (WDI) database, this paper examines whether the EU ETS has a spillover effect on PM2.5 damage reduction, and discusses the related impact mechanisms. The research results show that the EU ETS promotes the reduction of PM2.5 damage, and in different phases of implementation, the impact of the EU ETS on the reduction of PM2.5 damage has a dynamic effect. The robustness test results also show that the research conclusions of this paper are highly reliable. Finally, this paper gives relevant policy suggestions, which can encourage countries to achieve carbon emission reduction targets while helping to reduce PM2.5 damage, and eventually achieve a win-win situation between economic growth and environmental improvement.

Impact of posttranslational modifications in pancreatic carcinogenesis and treatments.

Pancreatic cancer (PC) is a highly aggressive cancer, with a 9% 5-year survival rate and a high risk of recurrence. In part, this is because PC is composed of heterogeneous subgroups with different biological and functional characteristics and personalized anticancer treatments are required. Posttranslational modifications (PTMs) play an important role in modifying protein functions/roles and are required for the maintenance of cell viability and biological processes; thus, their dysregulation can lead to disease. Different types of PTMs increase the functional diversity of the proteome, which subsequently influences most aspects of normal cell biology or pathogenesis. This review primarily focuses on ubiquitination, SUMOylation, and NEDDylation, as well as the current understanding of their roles and molecular mechanisms in pancreatic carcinogenesis. Additionally, we briefly summarize studies and clinical trials on PC treatments to advance our knowledge of drugs available to target the ubiquitination, SUMOylation, and NEDDylation PTM types. Further investigation of PTMs could be a critical field of study in relation to PC, as they have been implicated in the initiation and progression of many other types of cancer.

Does ecological compensation have a spillover effect on industrial structure upgrading? Evidence from China based on a multi-stage dynamic DID approach.

China's rapid economic development has led to increasingly serious environmental problems, such as the deterioration of its ecology in important river basins. Adjusting the industrial structure through the mechanism of ecological compensation (EC) is a key measure for solving this economic and environmental dilemma. Early research on the impact of ecological compensation mechanisms has mainly focused on evaluating their performance in terms of the ecological environment, with little empirical evidence. Therefore, it is necessary to explore the economic effects of ecological compensation mechanisms in order to achieve sustainable economic and environmental development. Based on panel data from the Xin'an River Basin in China from 2009 to 2018, a multistage dynamic difference-in-differences (DID) model was constructed to systematically study the impact of the ecological compensation mechanism on the upgrading of the industrial structure. The research results show that due to the implementation of the policy, the industrial structure in pilot ecological compensation areas tends to be rational and advanced. The ecological compensation policy has dynamic effects on the upgrading of the industrial structure during the different stages of its implementation. This study is conducive to further enriching the relevant theories and practices underlying the study of ecological compensation mechanisms. At the same time, this paper provides operational suggestions for ecological protection, the adjustment of the industrial structure, and the formulation of relevant macroeconomic policies.

Harnessing Hypoxia-Dependent Cyanine Photocages for In†Vivo Precision Drug Release.

Photocaging holds promise for the precise manipulation of biological events in space and time. However, current near-infrared (NIR) photocages are oxygen-dependent for their photolysis and lack of timely feedback regulation, which has proven to be the major bottleneck for targeted therapy. Herein, we present a hypoxia-dependent photo-activation mechanism of dialkylamine-substituted cyanine (Cy-NH) accompanied by emissive fragments generation, which was validated with retrosynthesis and spectral analysis. For the first time, we have realized the orthogonal manipulation of this hypoxia-dependent photocaging and dual-modal optical signals in living cells and tumor-bearing mice, making a breakthrough in the direct spatiotemporal control and in vivo feedback regulation. This unique photoactivation mechanism overcomes the limitation of hypoxia, which allows site-specific remote control for targeted therapy, and expands the photo-trigger toolbox for on-demand drug release, especially in a physiological context with dual-mode optical imaging under hypoxia.

Prediction on treatment improvement in depression with resting state connectivity: A coordinate-based meta-analysis.

BACKGROUND: Previous neuroimaging studies revealed abnormal resting-state functional connectivity between distributed brain areas in patients with major depressive disorder. Those abnormalities were normalized after treatment. Moreover, the functional connectivity could predict clinical response to those treatments. However, there has currently been no meta-analysis to verify these findings. METHODS: The current study aimed to investigate how the resting-state connectivity patterns predict antidepressant response to various treatments across depressive studies by using coordinate-based meta-analysis named activation likelihood estimation. The relevant articles were obtained by searching on PubMed and Web of Science. RESULTS: Following exclusion criteria of inappropriate studies, seventeen papers with 392 individual depressive patients were included. Those articles contained repetitive transcranial magnetic stimulation (rTMS) treatment, pharmacotherapy, cognitive behavioral therapy (CBT), electroconvulsive therapy (ECT) and transcutaneous vagus nerve stimulation in patients with depression. Meta-analysis revealed that clinical response to all treatments could be predicted by baseline default mode network connectivity in patients with depression. The rTMS treatment had larger effect size compared to other treatment strategies. Furthermore, subgroup meta-analysis showed that the baseline connectivity of perigenual anterior cingulate cortex (pgACC) and ventral medial prefrontal cortex could predict symptoms improvement of rTMS treatment. LIMITATIONS: More resting-state connectivity studies of CBT and ECT treatment are needed. CONCLUSIONS: This study highlighted crucial role of DMN, especially the pgACC, in understanding the underlying treatment mechanism of depression.

Clioquinol induces S-phase cell cycle arrest through the elevation of the calcium level in human neurotypic SH-SY5Y cells.

Clioquinol is recently considered to be the most promising drug for treating cancer and neurodegenerative diseases. However, its mode of action varies from different disease models. In this study, we found that clioquinol inhibited cell growth in human neurotypic SHSY-5Y cells, which was attributed to both S-phase cell-cycle arrest and autophagic cell death. Clioquinol increased the intracellular contents of iron and zinc as well as calcium as measured by ICP-AES. Staining of Fluo-3 confirmed an increase in the level of calcium. Analysis of the metal-binding ability of clioquinol showed that it was not a chelating agent of calcium ions and the elevation of intracellular calcium content is not achieved by clioquinol as an ionophore. CaCl2 could simulate or even aggravate the cytotoxicity of clioquinol and it increased S-phase cell cycle arrest induced by clioquinol in a concentration dependent manner. Staining of acridine orange demonstrated that autophagy induced by clioquinol was not affected by addition of calcium ions. In contrast, the intracellular calcium ion chelator BAPTA-am abolished the clioquinol-induced S phase arrest and reduced the cell death caused by clioquinol. The WB assay of cell cycle-related proteins (CDK2, p21 and p27) further confirmed that S phase arrest is positively correlated with intracellular calcium elevation, which was due to the alterations of the mRNA and protein levels of calcium pumps (SERCA and SPCA). Taken together, these data indicate that clioquinol regulates the level of intracellular calcium ions to induce S-phase cell cycle arrest in human SH-SY5Y cells. Our results demonstrate for the first time that an increase of intracellular calcium content is one of the mechanisms of clioquinol in the inhibition of human neurotypic SHSY-5Y cells.