N,N-dimethylformamide (DMF) is a universally used industrial material with exponential growth in production and consumption worldwide. The frequently reported occupational DMF poisoning cases in some ...countries and the gradually recognized unavoidable health risks to the general population highlight that DMF should still be a matter of concern. Previous studies have demonstrated that the liver is the primary target organ of DMF exposure and multiple mechanisms have been revealed. However, most of these studies investigate the detrimental effects of acute and subacute DMF exposure, while the effects of chronic DMF exposure are rarely studied. Furthermore, the key mechanism for the acute hepatotoxicity of DMF remains to be elucidated. Future research may focus on the identification of efficient preventive measures against the toxicity of DMF to occupational workers, the investigation of the detrimental effects of DMF at environmentally relevant doses, and the studies on the elimination and recycling of DMF in industrial wastes. Herein, we present an updated review of the metabolism of DMF, the biomarker of DMF exposure, underlying molecular mechanisms of DMF-induced hepatotoxicity, and the toxicity of DMF to both occupational workers and general populations and discuss the possible directions in future studies.
Software-Defined Networking (SDN) is an emerging networking paradigm that creates new opportunities for future generations of networks. The main characteristic of SDN is its ability to centralise ...control through the decoupling of control decisions from the network switches to make the network more flexible, programmable, and scalable. As part of this centralised control management, the SDN controller maintains a holistic view of the underlying network. Therefore, topology discovery in SDN is an essential service for topology-aware applications, such as routing, load balancing, mobility, and tracking. However, during the SDN topology discovery process, the controllers, without proper protection, are vulnerable to topology poisoning attacks, most notably Link Fabrication Attacks (LFAs). LFAs may be mounted due to a leak of packet source authentication, the lack of packet integrity checks, or the reuse of static packets. In this paper, we describe an effective and scalable security framework, LINK-GUARD, used for facilitating secure link discoveries in an SDN network. LINK-GUARD is designed to detect and thwart LFAs, thus reducing the risks of network topology poisoning. The framework has been implemented and evaluated on a Mininet emulator with an RYU controller. The security analysis indicates that LINK-GUARD can effectively and efficiently secure topology discoveries against both host-based and switch-based link fabrication attacks. Performance evaluation results show that the legitimacy of new links can be verified nearly real-time, taking approximately 30 milliseconds, and fake links can be detected within as low as 6 milliseconds, with a negligible runtime overhead. These results show that LINK-GUARD is a scalable solution for dynamic and large SDN networks.
Transient receptor potential (TRP) channels are sensors for a variety of cellular and environmental signals. Mammals express a total of 28 different TRP channel proteins, which can be divided into ...seven subfamilies based on amino acid sequence homology: TRPA (Ankyrin), TRPC (Canonical), TRPM (Melastatin), TRPML (Mucolipin), TRPN (NO-mechano-potential, NOMP), TRPP (Polycystin), TRPV (Vanilloid). They are a class of ion channels found in numerous tissues and cell types and are permeable to a wide range of cations such as Ca
, Mg
, Na
, K
, and others. TRP channels are responsible for various sensory responses including heat, cold, pain, stress, vision and taste and can be activated by a number of stimuli. Their predominantly location on the cell surface, their interaction with numerous physiological signaling pathways, and the unique crystal structure of TRP channels make TRPs attractive drug targets and implicate them in the treatment of a wide range of diseases. Here, we review the history of TRP channel discovery, summarize the structures and functions of the TRP ion channel family, and highlight the current understanding of the role of TRP channels in the pathogenesis of human disease. Most importantly, we describe TRP channel-related drug discovery, therapeutic interventions for diseases and the limitations of targeting TRP channels in potential clinical applications.
Colorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel ...subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment.
A consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments.
Four distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells.
Ion channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.
The low-carbon power transition, which is key to combatting climate change, has far-reaching effects on achieving the Sustainable Development Goals (SDGs) in terms of issues such as resource use, ...environmental emissions, employment, and many more. Here, we assess the potential impacts of the power transition on progress toward achieving multiple SDGs (covering 18 targets across the 17 goals) across 49 economies under nine socioeconomic and climate scenarios. We find that the low-carbon power transition under the representative concentration pathway (RCP)2.6 scenarios could lead to an approximately 11% improvement in the global SDG index score from 54.70 in 2015 to 59.89-61.33 in 2100. However, the improvement would be significantly decreased to 4.42%-7.40% and 7.55%-8.93% under the RCP6.0 and RCP4.5 scenarios, respectively. The power transition could improve the overall SDG index in most developed economies under all scenarios while undermining their resource-related SDG scores. Power transition-induced changes in international trade would improve the SDG progress of developed economies but jeopardize that of developing economies, which usually serve as resource hubs for meeting the demand for low-carbon power transition in developed economies.
Poly(ethylene glycol) (PEG) is the most widely used polymer to decorate inorganic nanoparticles (NPs) by the “grafting-to” method for antifouling properties. PEG also shows diverse supramolecular ...interactions with nanoparticle surfaces and polar molecules, suggesting that the physisorption between PEG chains and NPs cannot be ignored in the “grafting-to” process. However, the effect of physisorption of PEG to NPs on the process of chemisorption has been rarely studied. Herein, we report that unfunctionalized PEG is physically adsorbed on various NPs by polyvalent supramolecular interactions, adopting “loop-and-train-tail” conformations. We investigated the effect of molecular weight of PEG and ligands of the NPs on the conformation of PEG chains by experimental methods and simulation. It is demonstrated that the physisorption of PEG on NPs can facilitate the chemisorption in the initial stages but delays it in the later stages during the “grafting-to” process. This work provides a deeper understanding of the conformation of physisorbed PEG on NPs and the relationship between physisorption and chemisorption.
Ginsenosides, the major compounds present in ginseng, are known to have numerous physiological and pharmacological effects. The physiological processes, enzymes and genes involved in ginsenoside ...synthesis in
have been well characterized. However, relatively little information is known about the dynamic metabolic changes that occur during ginsenoside accumulation in ginseng. To explore this topic, we isolated metabolites from different tissues at different growth stages, and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS). The results showed that a total of 30, 16, 20, 36 and 31 metabolites were identified and involved in different developmental stages in leaf, stem, petiole, lateral root and main root, respectively. To investigate the contribution of tissue to the biosynthesis of ginsenosides, we examined the metabolic changes of leaf, stem, petiole, lateral root and main root during five development stages: 1-, 2-, 3-, 4- and 5-years. The score plots of partial least squares-discriminate analysis (PLS-DA) showed clear discrimination between growth stages and tissue samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis in the same tissue at different growth stages indicated profound biochemical changes in several pathways, including carbohydrate metabolism and pentose phosphate metabolism, in addition, the tissues displayed significant variations in amino acid metabolism, sugar metabolism and energy metabolism. These results should facilitate further dissection of the metabolic flux regulation of ginsenoside accumulation in different developmental stages or different tissues of ginseng.
Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death in intensive care units. The development of sepsis-associated organ ...dysfunction (SAOD) poses a threat to the survival of patients with sepsis. Unfortunately, the pathogenesis of sepsis and SAOD is complicated, multifactorial, and has not been completely clarified. Recently, numerous studies have demonstrated that pyroptosis, which is characterized by inflammasome and caspase activation and cell membrane pore formation, is involved in sepsis. Unlike apoptosis, pyroptosis is a pro-inflammatory form of programmed cell death that participates in the regulation of immunity and inflammation. Related studies have shown that in sepsis, moderate pyroptosis promotes the clearance of pathogens, whereas the excessive activation of pyroptosis leads to host immune response disorders and SAOD. Additionally, transcription factors, non-coding RNAs, epigenetic modifications and post-translational modifications can directly or indirectly regulate pyroptosis-related molecules. Pyroptosis also interacts with autophagy, apoptosis, NETosis, and necroptosis. This review summarizes the roles and regulatory mechanisms of pyroptosis in sepsis and SAOD. As our understanding of the functions of pyroptosis improves, the development of new diagnostic biomarkers and targeted therapies associated with pyroptosis to improve clinical outcomes appears promising in the future.
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