OBJECTIVE: Pathways of transitioning from tobacco smoking to vaping after receiving an e-cigarette-based smoking cessation intervention have been minimally explored.
OBJECTIVE: 1) identify pathways between intervention delivery and final follow-up; 2) describe baseline and post-intervention statistical data in relation to smoking/vaping behaviour of the different pathway groups; 3) explore qualitative participant perspectives contextualising pathway groups.
METHODS: Embedded mixed-methods analysis of data collected for the Cessation of Smoking Trial in the Emergency Department (COSTED) randomised controlled trial.
METHODS: Recruitment from 6 Emergency Departments (5 in England and 1 in Scotland) between January and August 2022.
METHODS: 366 adult smokers who were randomised to receive the COSTED intervention and provided data at 6-month follow-up. Qualitative subsample of 24 participants interviewed after follow-up.
METHODS: Brief smoking cessation advice, provision of an e-cigarette starter kit and referral to the local Stop Smoking Service.
METHODS: Descriptive statistical reporting of identified pathways and smoking/vaping behaviour at baseline and 6-month follow-up. Semi-structured phone/video interviews analysed thematically.
RESULTS: 13.4% (n = 49) of participants quit smoking within 1 month of receiving the intervention, 19.1% (n = 70) quit between 1 and 6 months, 24.9% (n = 91) reduced cigarettes per day (CPD) by at least 50%, and 42.6% did not experience a significant smoking reduction. Approximately a third of participants who quit reported not vaping at follow-up. Reporting dual use was associated with a reduction in CPD. Appoximately a third reported experimenting with a different device to the one provided as part of the intervention. Quitters reported themes of satisfaction with vaping, changes in environment facilitating quitting and motivation to quit.
CONCLUSIONS: Dual use of cigarettes and e-cigarettes can result in a reduction of smoking and may preclude quitting smoking. Sustained e-cigarette use is not always necessary for quitting success. Success depends on personal context as well satisfaction with vaping.

Inflammation is a normal immune response in organisms, but it often triggers chronic diseases such as colitis and arthritis. Currently, the most widely used anti-inflammatory drugs are non-steroidal anti-inflammatory drugs, albeit they are accompanied by various adverse effects such as hypertension and renal dysfunction. Bioactive peptides (BAPs) provide therapeutic benefits for inflammation and mitigate side effects. Herein, this review focuses on the therapeutic effects of various BAPs on inflammation in different body parts. Emphasis is placed on the immunomodulatory mechanisms of BAPs in treating inflammation, such as regulating the release of inflammatory mediators, modulating MAPK and NF-κB signaling pathways, and reducing oxidative stress reactions for immunomodulation. This review aims to provide a reference for the function, application, and anti-inflammation mechanisms of BAPs.

Peroxiredoxins (Prxs) are members of the antioxidant enzymes necessary for every living object in the three domains of life and play critical roles in controlling peroxide levels in cells. This comprehensive literature review aims to elucidate the peroxidase activity of Prxs, examining their roles and significance for organisms across various taxa. Ironically, the primary role of the Prxs is the peroxidase activity, which comprises the reduction of hydrogen peroxide and other organic hydroperoxides and decreases the risk of oxidative damage in the cells. The above enzymatic activity occurs through the reversible oxidation-reduction catalyzed by cysteine residues in the active site by forming sulfenic acid and reduction by intracellular reductants. Structurally and functionally, Prxs function as dimers or decamers and show different catalytic patterns according to their subfamilies or cellular compartments. Compared to the mechanisms of the other two subgroups of Prxs, including 2-Cys Prxs and atypical Prxs, the 1-Cys Prxs have monomer-dimer switch folding coupled with catalytic activity. In addition to their peroxidase activity, which is widely known, Prxs are becoming acknowledged to be involved in other signaling processes, including redox signaling and apoptosis. This aversion to oxidative stress and regulation by the cellular redox state places them at the heart of adaptive cellular responses to changes in the environment or manifestations of diseases. In conclusion, based on the data obtained and on furthering the knowledge of Prxs\' structure and function, these enzymes may be classified as a diverse yet essential family of proteins that can effectively protect cells from the adverse effects of oxidative stress due to peroxidase activity. This indicates secondary interactions, summarized as peroxide detoxification or regulatory signaling, and identifies their applicability in multiple biological pathways. Such knowledge is valuable for enhancing the general comprehension of essential cellular functions and disclosing further therapeutic approaches to the diseases caused by the increased production of reactive oxygen species.

BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach.
RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or HF hospital admission. We also assessed the relationship of each SASP factor to 4746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Two SASP factors were identified. Both factors were associated with older age, lower estimated glomerular filtration rate, and more advanced New York Heart Association class, among other clinical variables. Both SASP factors exhibited a significant positive association with the risk of death independent of the Meta-Analysis of Global-Group in Chronic HF score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The 2 identified SASP factors were associated with 1201 and 1554 proteins, respectively, belonging to various pathways including the coagulation system, complement system, acute phase response signaling, and retinoid X receptor-related pathways that regulate cell metabolism.
CONCLUSIONS: Increased SASP components are independently associated with adverse outcomes in HF. Biologic pathways associated with SASP are predominantly related to coagulation, inflammation, and cell metabolism.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injures the pork products and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and the host immune system, along with the involvement of virulence-related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Janus Kinase (JAK) and JAK Signal Transducers and Activators of Transcription (STAT), apoptosis, and other modulation. The aim is to summarize the dynamic process during ASFV infection and entry into the host cell, provide a rational insight into development of a vaccine, and provide a better clear knowledge of how ASFV impacts the host.

OBJECTIVE: Peritoneal infection, due to anastomotic leakage, after resection for colorectal cancer have been shown to associate with increased cancer recurrence and mortality, as well as cardiovascsular morbidity. Alterations in circulating protein levels could help shed light on the underlying mechanisms, prompting this exploratory study of 64 patients operated for colorectal cancer with anastomosis.
METHODS: Thirty-two cases who suffered a postoperative peritoneal infection were matched with 32 controls who had a complication-free postoperative stay. Proteins in serum samples at their first postoperative visit and at one year after surgery were analysed using proximity extension assays and enzyme-linked immunosorbent assays. Multivariate projection methods, adjusted for multiple testing, were used to compare levels between groups, and enrichment and network analyses were performed.
RESULTS: Seventy-seven proteins, out of 270 tested, were differentially expressed at a median sampling time of 41 days postoperatively. These proteins were all normalised one year after surgery. Many of the differentially expressed top hub proteins have known involvement in cancer progression, survival, invasiveness and metastasis. Over-represented pathways were related to cardiomyopathy, cell-adhesion, extracellular matrix, phosphatidylinositol-3-kinase/Akt (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling.
CONCLUSIONS: These affected proteins and pathways could provide clues as to why patients with peritoneal infection might suffer increased cancer recurrence, mortality and cardiovascular morbidity.

UNASSIGNED: Identifying molecular mechanisms responsible for the response to heat stress is essential to increase production, reproduction, health, and welfare. This study aimed to identify early biological responses and potential biomarkers involved in the response to heat stress and animal\'s recovery in tropically adapted beef cattle through proteomic analysis of blood plasma.
UNASSIGNED: Blood samples were collected from 14 Caracu males during the heat stress peak (HSP) and 16 h after it (heat stress recovery-HSR) assessed based on wet bulb globe temperature index and rectal temperature. Proteome was investigated by liquid chromatography-tandem mass spectrometry from plasma samples, and the differentially regulated proteins were evaluated by functional enrichment analysis using DAVID tool. The protein-protein interaction network was evaluated by STRING tool.
UNASSIGNED: A total of 1,550 proteins were detected in both time points, of which 84 and 65 were downregulated and upregulated during HSR, respectively. Among the differentially regulated proteins with the highest absolute log-fold change values, those encoded by the GABBR1, EPHA2, DUSP5, MUC2, DGCR8, MAP2K7, ADRA1A, CXADR, TOPBP1, and NEB genes were highlighted as potential biomarkers because of their roles in response to heat stress. The functional enrichment analysis revealed that 65 Gene Ontology terms and 34 pathways were significant (P < 0.05). We highlighted those that could be associated with the response to heat stress, such as those related to the immune system, complement system, hemostasis, calcium, ECM-receptor interaction, and PI3K-Akt and MAPK signaling pathways. In addition, the protein-protein interaction network analysis revealed several complement and coagulation proteins and acute-phase proteins as important nodes based on their centrality and edges.
UNASSIGNED: Identifying differentially regulated proteins and their relationship, as well as their roles in key pathways contribute to improve the knowledge of the mechanisms behind the response to heat stress in naturally adapted cattle breeds. In addition, proteins highlighted herein are potential biomarkers involved in the early response and recovery from heat stress in tropically adapted beef cattle.

Metabolism is the network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting KEGG Level 2 pathway category involvement of metabolites based on their chemical structure. Here, we present the first machine learning model to predict metabolite association to more granular KEGG Level 3 metabolic pathways. We used a feature and dataset engineering approach to generate over one million metabolite-pathway entries in the dataset used to train a single binary classifier. This approach produced a mean Matthews correlation coefficient (MCC) of 0.806 ± 0.017 SD across 100 cross-validations iterations. The 172 Level 3 pathways were predicted with an overall MCC of 0.726. Moreover, metabolite association with the 12 Level 2 pathway categories were predicted with an overall MCC of 0.891, representing significant transfer learning from the Level 3 pathway entries. These are the best metabolite-pathway prediction results published so far in the field.

OBJECTIVE: Loss of expression of tumour suppressor PAX2 and MMR deficiency (dMMR) has been frequently seen in endometrial endometrioid adenocarcinoma (EEC). However, the relationship between PAX2 expression and MMR status is unknown.
RESULTS: We studied the PAX2 expression and examined its association with MMR status at the protein and genetic levels in 180 cases of EEC. Overall, total loss of PAX2 expression was found in about 70%, while retained PAX2 expression was seen in 30% of EEC. Among 125 cases with loss of PAX2, 68.8% were found in EECs with pMMR, while 31.2% were seen in those with dMMR. Among 55 cases of EECs with retained PAX2 expression, 92.7% were EECs with dMMR and 7.3% were those with pMMR (P < 0.001). While dMMR cases with MLH1 hypermethylation show almost equal retained or loss of PAX2 expression (52% versus 48%), dMMR with genetic alterations had significantly more retained PAX2 expression than loss of PAX2 (92.3% versus 7.7%), regardless of somatic or germline mutations. Loss of PAX2 was observed in 97.3% of dMMR with MLH1 hypermethylation compared to 2.7% of dMMR with genetic alterations (P < 0.001). Aggressive features such as higher tumour grades (FIGO 2-3) and advanced clinical stage (T2-T4) were significantly more frequently seen in dMMR with retained PAX2 expression, compared those to pMMR with loss of PAX2 expression.
CONCLUSIONS: Our study demonstrates a close correlation between retained PAX2 expression and dMMR in EEC. The molecular mechanism and clinical significance linking these two pathways in EEC remains to be unravelled.

The Pew Charitable Trust\'s 2020 report \'Breaking the Plastic Wave\', indicates that existing technologies could support an 80% reduction in plastic leakage relative to business as usual by 2040. Therefore, South Africa became the first country to work with the Pew Charitable Trust and Oxford University to test and apply \'Pathways\', a modelling framework and software tool which stemmed and evolved from the Pew report, at country level. The tool calculates the flows of plastics in the economy and the impact of various strategies to reduce future plastic pollution. The Scenario Builder within the Pathways tool allows the user to optimise flows in the plastics value chain to satisfy a set of defined objectives in order to achieve an optimal solution. Three major findings have emerged from the application of Pathways at country level for South Africa. Firstly, plastic pollution is set to almost double by 2040 if no interventions are implemented. Secondly, meeting the newly legislated extended producer responsibility (EPR) targets set for plastic packaging can avoid 33% of projected total pollution over the period of 2023-2040. Lastly, an optimal system change can avoid 63% of total plastic pollution over the period 2023-2040. Thus, applying Pathways at country level in South Africa has proven to be valuable by setting a baseline against which progress towards reducing plastic pollution can be measured; determining the outcome of meeting the legislated EPR targets over time, and informing policy decisions by allowing users to model different scenarios towards an optimal system change scenario.