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PurposeTo explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved.MethodsNew Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA).ResultsDifferent molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following.ConclusionsIn the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.

Abstract It is long been suggested that one‐carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small‐molecule kenpaullone (KEN) promoted ADAM10 translation via the 5′ untranslated region (5′UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5′UTR‐interacting RNA binding protein (RBP), mediated KEN‐induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5′UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5′UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 “moonlighted” as RBP by binding to GAGGG motif and promoting the 5′UTR‐dependent ADAM10 translation initiation.

Abstract Assessing and improving energy efficiency is crucial for addressing the problems of climate change and global warming. This study evaluates the performance of each Organisation for Economic Cooperation and Development (OECD) nation based on the weights obtained by Data Envelopment Analysis (DEA), combined with a modified Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method based on the concept of the aspiration level (called modified TOPSIS-AL). Objective weights are obtained for each country through DEA. This method offers an effective improvement over the previous methods which only use the same subjective weights for the calculation. In addition, our model is also able to account for negative environmental externalities generated during development and provides a comprehensive assessment system for the evaluation of national sustainable development. The findings indicate that the member nations are gradually adopting policies to reduce fossil fuel consumption. However, regional analysis showed that the overall performance of the G7 nations differed significantly from that of the non-G7 nations. The importance of this study lies in the fact that energy consumption not only creates environmental burdens but also affects resource production patterns and productivity. By evaluating the performance of nations in terms of energy efficiency and environmental impact, we aim to address the challenges posed by energy consumption for sustainable development. The proposed hybrid model offers several advantages, including a comprehensive assessment system, consideration of negative externalities, and practical policy recommendations.

Abstract Background Colorectal cancer (CRC) is a worldwide cancer with rising annual incidence. New medications for patients with CRC are still needed. Recently, fluorescent chemical probes have been developed for cancer imaging and therapy. Signal transducer and activator of transcription 1 (STAT1) has complex functions in tumorigenesis and its role in CRC still needs further investigation. Methods RNA sequencing datasets in the NCBI GEO repository were analyzed to investigate the expression of STAT1 in patients with CRC. Xenograft mouse models, tail vein injection mouse models, and azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were generated to study the roles of STAT1 in CRC. A ligand-based high-throughput virtual screening approach combined with SWEETLEAD chemical database analysis was used to discover new STAT1 inhibitors. A newly designed and synthesized fluorescently labeled 4’,5,7-trihydroxyisoflavone (THIF) probe (BODIPY-THIF) elucidated the mechanistic actions of STAT1 and THIF in vitro and in vivo. Colonosphere formation assay and chick chorioallantoic membrane assay were used to evaluate stemness and angiogenesis, respectively. Results Upregulation of STAT1 was observed in patients with CRC and in mouse models of AOM/DSS-induced CRC and metastatic CRC. Knockout of STAT1 in CRC cells reduced tumor growth in vivo. We then combined a high-throughput virtual screening approach and analysis of the SWEETLEAD chemical database and found that THIF, a flavonoid abundant in soybeans, was a novel STAT1 inhibitor. THIF inhibited STAT1 phosphorylation and might bind to the STAT1 SH2 domain, leading to blockade of STAT1-STAT1 dimerization. The results of in vitro and in vivo binding studies of THIF and STAT1 were validated. The pharmacological treatment with BODIPY-THIF or ablation of STAT1 via a CRISPR/Cas9-based strategy abolished stemness and angiogenesis in CRC. Oral administration of BODIPY-THIF attenuated colitis symptoms and tumor growth in the mouse model of AOM/DSS-induced CRC. Conclusions This study demonstrates that STAT1 plays an oncogenic role in CRC. BODIPY-THIF is a new chemical probe inhibitor of STAT1 that reduces stemness and angiogenesis in CRC. BODIPY-THIF can be a potential tool for CRC therapy as well as cancer cell imaging.

This study aims to explore the comparison of the regional competitiveness of the nations targeted by Taiwan’s New Southbound Policy and the key indicators that influence regional competitiveness. Through comparative analysis between each other, we will further select countries and regions that are most suitable for investment and exchange. Regional competitiveness describes the ability of various economies to compete for resources or markets in a region. Exploring regional competitiveness allows the best nations for investment to be identified so that unnecessary costs and losses may be avoided. This paper proposes a multiple attribute decision making method, grey relational analysis (GRA), for solving this kind of problem. This study investigates the regional competitiveness of various nations using competitiveness rankings obtained through the ranking of grey relational ordinals. The study seeks to identify critical factors underlying regional competitiveness. The study variables are grouped into four major factors: economy, human resources, technology, and trade capability. The results reveal that India, Singapore, and Australia are nations with regional competitive advantages. Labor force and technology are indispensable factors for enhancing regional competitiveness. ASEAN countries have greater regional competitiveness than South Asia or Australia and New Zealand. First published online 09 June 2022