Replacing Traditional Plastics with Biodegradable Plastics:Impact on Carbon Emissions

In recent years, a great deal of attention has been focused on the environmental impact of plastics, including the carbon emissions related to plastics, which has promoted the application of biodegradable plastics. Countries worldwide have shown high interest in replacing traditional plastics with biodegradable plastics. However, no systematic comparison has been conducted on the carbon emissions of biodegradable versus traditional plastic products. This study evaluates the carbon emissions of traditional and biodegradable plastic products (BPPs) over four stages and briefly discusses environmental and economic perspectives. Four scenarios—namely, the traditional method, chemical recycling, industrial composting, and anaerobic digestion—are considered for the disposal of waste biodegradable plastic product (WBBPs). The analysis takes China as a case study. The results show that the carbon emissions of 1000 traditional plastic products (plastic bags, lunch boxes, cups, etc.) were 52.09–150.36 carbon emissions equivalent of per kilogram (kg CO2eq), with the stage of plastic production contributing 50.71%–50.77%. In comparison, 1000 similar BPPs topped out at 21.06–56.86 kg CO2eq, approximately 13.53%–62.19% lower than traditional plastic products. The difference was mainly at the stages of plastic production and waste disposal, and the BPPs showed significant carbon reduction potential at the raw material acquisition stage. Waste disposal plays an important role in environmental impact, and composting and anaerobic digestion are considered to be preferable disposal methods for WBBPs. However, the high cost of biodegradable plastics is a challenge for their widespread use. This study has important reference significance for the sustainable development of the biodegradable plastics industry.</p

The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism

The human proton-coupled folate transporter (PCFT; SLC46A1) or hPCFT was identified in 2006 as the principal folate transporter involved in the intestinal absorption of dietary folates. A rare autosomal recessive hereditary folate malabsorption syndrome is attributable to human SLC46A1 variants. The recognition that hPCFT was highly expressed in many tumors stimulated substantial interest in its potential for cytotoxic drug targeting, taking advantage of its high-level transport activity under acidic pH conditions that characterize many tumors and its modest expression in most normal tissues. To better understand the basis for variations in hPCFT levels between tissues including human tumors, studies have examined the transcriptional regulation of hPCFT including the roles of CpG hypermethylation and critical transcription factors and cis elements. Additional focus involved identifying key structural and functional determinants of hPCFT transport that, combined with homology models based on structural homologies to the bacterial transporters GlpT and LacY, have enabled new structural and mechanistic insights. Recently, cryo-electron microscopy structures of chicken PCFT in a substrate-free state and in complex with the antifolate pemetrexed were reported, providing further structural insights into determinants of (anti)folate recognition and the mechanism of pH-regulated (anti)folate transport by PCFT. Like many major facilitator proteins, hPCFT exists as a homo-oligomer, and evidence suggests that homo-oligomerization of hPCFT monomeric proteins may be important for its intracellular trafficking and/or transport function. Better understanding of the structure, function and regulation of hPCFT should facilitate the rational development of new therapeutic strategies for conditions associated with folate deficiency, as well as cancer

Biology and therapeutic applications of the proton-coupled folate transporter

Introduction: The proton-coupled folate transporter (PCFT; SLC46A1) was discovered in 2006 as the principal mechanism by which folates are absorbed in the intestine and the causal basis for hereditary folate malabsorption (HFM). In 2011, it was found that PCFT is highly expressed in many tumors. This stimulated interest in using PCFT for cytotoxic drug targeting, taking advantage of the substantial levels of PCFT transport and acidic pH conditions commonly associated with tumors. Areas covered: We summarize the literature from 2006 to 2022 that explores the role of PCFT in the intestinal absorption of dietary folates and its role in HFM and as a transporter of folates and antifolates such as pemetrexed (Alimta) in relation to cancer. We provide the rationale for the discovery of a new generation of targeted pyrrolo[2,3-d]pyrimidine antifolates with selective PCFT transport and inhibitory activity toward de novo purine biosynthesis in solid tumors. We summarize the benefits of this approach to cancer therapy and exciting new developments in the structural biology of PCFT and its potential to foster refinement of active structures of PCFT-targeted anti-cancer drugs. Expert opinion: We summarize the promising future and potential challenges of implementing PCFT-targeted therapeutics for HFM and a variety of cancers

Therapeutic targeting of mitochondrial one-carbon metabolism in cancer

One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation. 1C pathways are compartmentalized in the cytosol, mitochondria, and nucleus. 1C metabolism in the cytosol has been an important therapeutic target for cancer since the inception of modern chemotherapy, and “antifolates” targeting cytosolic 1C pathways continue to be a mainstay of the chemotherapy armamentarium for cancer. Recent insights into the complexities of 1C metabolism in cancer cells, including the critical role of the mitochondrial 1C pathway as a source of 1C units, glycine, reducing equivalents, and ATP, have spurred the discovery of novel compounds that target these reactions, with particular focus on 5,10-methylene tetrahydrofolate dehydrogenase 2 and serine hydroxymethyltransferase 2. In this review, we discuss key aspects of 1C metabolism, with emphasis on the importance of mitochondrial 1C metabolism to metabolic homeostasis, its relationship with the oncogenic phenotype, and its therapeutic potential for cancer

Development and validation of chemical features-based proton-coupled folate transporter/activity and reduced folate carrier/activity models (pharmacophores)

All clinically used antifolates lack transport selectivity for tumors over normal cells resulting in dose-limiting toxicities. There is growing interest in developing novel tumor-targeted cytotoxic antifolates with selective transport into tumors over normal cells via the proton-coupled folate transporter (PCFT) over the ubiquitously expressed reduced folate carrier (RFC). A lack of X-ray crystal structures or predictive models for PCFT or RFC has hindered structure-aided drug design for PCFT-selective therapeutics. Four-point validated models (pharmacophores) were generated for PCFT/Activity (HBA, NI, RA, RA) and RFC/Activity (HBD, NI, HBA, HBA) based on inhibition (IC 50 ) of proliferation of isogenic Chinese hamster ovary (CHO) cells engineered to express only human PCFT or only RFC. Our results revealed substantial differences in structural features required for transport of novel molecules by these transporters which can be utilized for developing transporter-selective antifolates

Dicer induced reactive oxygen species inhibit hepatocellular carcinoma through interacting with cytochrome c oxidase

AbstractDicer is an RNaseIII in microRNA processing that modulates multiple biological processes including tumorigenesis. We have shown that Dicer could inhibit the growth of hepatocellular carcinoma (HCC) previously [Zhang L, Wang C, Liu S, Zhao Y, et al. Oncol Lett 2016;11:3961-3966]. Here, we evaluated the relationships between Dicer and reactive oxygen species (ROS) as well as their modulation for HCC. We found Dicer expression was positively associated with ROS generation in HCC tissue at borderline statistical levels (p = .065); functional analysis showed Dicer could both induce the ROS generation (p < .01) and reduce the activity of Cytochrome c Oxidase (COX) (p < .05) by comparing the Dicer transfected and control HCC cells. The COX inhibitor ADDA-5 hydrochloride could increase the ROS generation, whereas the ROS scavenger N-acetylcysteine (NAC) could decrease the COX activity. Further analysis also demonstrated that one kind of ROS, H2O2, could repress the proliferation and migration as well as increase the apoptosis of HCC cells. Our data indicated that Dicer could inhibit the HCC growth by promoting ROS generation; ROS and COX interacted with each other to modify this process