Kratom (Mitragyna speciosa), a tropical plant from Southeast Asia, is known for its complex alkaloid profile and dose-dependent neurobiological effects. Traditionally used for pain relief and as a stimulant, its principal alkaloids, like mitragynine and 7-OH mitragynine, interact with opioid, serotonergic, and dopaminergic systems. Low doses produce stimulant effects, while higher doses yield analgesic and sedative actions, impacting neurotransmitters such as dopamine and modulating reward pathways. Recent research underscores kratom’s intricate pharmacology, including biased opioid receptor signalling and potential cognitive consequences at higher doses. While kratom may influence mood, memory, and executive function, much evidence remains preclinical, with translational challenges. Higher doses have been linked to cognitive impairment and possible organ toxicity, particularly hepatotoxicity, though confounding by concurrent substance use complicates clinical interpretation. This review examines the pharmacodynamics of kratom alkaloids within mesolimbic, hippocampal, and prefrontal circuits, highlighting both therapeutic potential and associated risks.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder with undefined mechanisms, no diagnostic tools and treatments. To investigate concurrent system dysfunctions, we recruited age- and sex-matched ME/CFS patients and healthy controls for a multimodal analysis of energy metabolism, immune profiles, and plasma proteomics. Immune cells from ME/CFS patients show elevated adenosine monophosphate (AMP) and adenosine diphosphate (ADP) with a reduced ATP/ADP ratio, indicating decreased ATP generation and cellular energy stress. Immune profiling reveals skewing toward less mature effector subsets of CD4+, CD8+, and γδ T cells, with reduced CD1c+CD141- conventional DC type 2 and CD56lowCD16+ terminal natural killer cells. Elevated levels of plasma proteins associated with thrombus formation and vascular reactivity may contribute to the endothelial dysfunction observed in ME/CFS patients. Classification and regression tree modeling identifies variables with strong predictive potential for ME/CFS. Together, this study provides insights into the somatic symptoms and underlying biology of ME/CFS.

BACKGROUND AND OBJECTIVES:Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration. METHODS:To gain insights into the links between the KP and neurodegeneration in MS, we investigated the KP metabolomics profile of relapsing remitting MS (RRMS) patients and their correlation with parameters of neurodegeneration in brain and retinal. Outpatients with a clinical diagnosis of RRMS (n = 98) or age-matched and sex-matched healthy controls (n = 39) were included. MS participants undertook yearly evaluation of MRI and optical coherence tomography scan to evaluate neuroaxonal loss. Blood samples were collected at the baseline from all participants for the biochemical analysis of KP metabolites. RESULTS:We identified increased plasma levels of AA and 3HAA in the MS group, indicating an anti-inflammatory response alongside active neurodegeneration. By contrast, plasma levels of KYNA and 3HK were lower in the MS group than in healthy controls. Our analysis revealed a higher KYN:tryptophan (TRP) and QUIN:KYNA ratios in the MS cohort, suggesting activation of the pathway toward the production of neurotoxic QUIN. Another important finding was that KP metabolites were correlated with measures of axonal degeneration in patients with MS. Notably, central brain atrophy positively correlated with the TRP levels, but negatively correlated with KYN and level KYN:TRP ratio. Finally, the choroid plexus volume was inversely correlated with KYNA plasma levels. DISCUSSION:These findings highlight changes in the biosynthesis of KP during the progression of RRMS and its correlation with axonal loss. This study underscores the potential of targeting the KP in developing novel treatments for neuroaxonal damage in MS and warrants future research in greater depth.

BackgroundCSF and blood soluble TREM2 (sTREM2) levels have been found to increase at early stage of Alzheimer's disease (AD). The relationships between sTREM2, AD-related biomarkers, and other neuroinflammation biomarkers remain unclear. Moreover, the impact of rare variants in TREM2 gene (R47H/R62H), which are associated with increased risk of AD, on plasma sTREM2 has not been elucidated.ObjectiveInvestigate the association of plasma sTREM2 levels with brain amyloid-β (Aβ) load and AD-related blood biomarkers, i.e., phosphorylated tau (pTau)-181, pTau-231, GFAP, NFL, and other neuroinflammation and peripheral inflammation markers in cognitively normal (CN) older adults at risk of AD (CN Aβ+) compared to CN Aβ-, including the effect of AD-linked TREM2 rare variants.MethodsPlasma sTREM2 concentrations were measured by MesoScale Discovery (MSD) assay from the KARVIAH cohort. Participants underwent cognitive tests and PET amyloid imaging. Genetic data and blood biomarkers were included for correlation analysis. Associations with plasma sTREM2 were investigated upon stratification by PET-Aβ load SUVR ((CN Aβ- (n = 65) and CN Aβ+ (n = 35)) as the main analysis. A subgroup analysis based on the TREM2 R47H and R62H genotype was conducted as exploratory analysis.ResultsPlasma sTREM2 positively correlated with plasma pTau181, and pTau231 in CN Aβ+ group. Plasma sTREM2 positively correlated with serum microglial kynurenine pathway metabolites. Plasma sTREM2 and brain Aβ load were higher in R47H TREM2 carriers compared to non-carriers.ConclusionsOur findings suggest plasma sTREM2 relates to downstream tau processes in amyloid-positive individuals, providing novel insights into the roles of peripheral TREM2 signaling that reflects microglial activity in early AD neuropathological development.

The central nervous system (CNS) relies on complex and dynamic interactions between neurons and glial cells. Among glial cells, astrocytes regulate the chemical environment surrounding neurons and supply essential nutrients for brain metabolism whereas microglia, the resident macrophages of the CNS, play critical roles in homeostasis, defense, and responses to injury. Both microglia and astrocytes contribute to the regulation of excitotoxicity and inflammation mediated by the metabolism of tryptophan (Trp) via the kynurenine pathway. Trp metabolism generates several bioactive metabolites, including quinolinic acid (QUIN) and kynurenic acid (KYNA), which have opposing effects. QUIN, produced by activated microglia, acts as an agonist for NMDA receptors; excessive stimulation of these receptors can lead to excitotoxicity and neuronal death. Conversely, KYNA, primarily produced by astrocytes via kynurenine 2,3-aminotransferases (KAT), acts as an NMDA receptor antagonist, conferring neuroprotection by mitigating excitotoxicity. Dysregulation of the Trp metabolism is implicated in many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis, as well as in various neuropsychiatric disorders. This review examines the cellular and molecular mechanisms underlying Trp metabolism in glial cells, highlighting the unique contributions of each glial phenotype, the implications for CNS pathologies, and the potential biomarkers and therapeutic targets for restoring homeostasis and preventing disease progression.

INTRODUCTION:Metastasis remains the major cause of death in breast cancer (BrCa) and lacks specific treatment strategies. The kynurenine pathway (KP) has been suggested as a key mechanism facilitating progression of BrCa. While KP activity has been explored in primary BrCa, its role in metastasis remains unclear. To better understand this, we examined changes in the KP of BrCa with no metastasis compared to BCa that produced local or distant metastases. Given that the cancer cell secretome plays a role in metastasis, we also investigated the relationship between changes in KP activity and serum proteins of patients with local or distant metastases. METHODS:To investigate changes in the KP in BrCa, with and without metastasis, we quantified KP metabolites in blood sera collected from patients with stage 1 BrCa (n = 34), BrCa with local metastases (n = 46), BrCa with distant metastases (n = 20) and healthy controls (n = 39). The serum protein profile of the BrCa patients with local or distant metastasis was determined before correlation analyses were carried out to examine the relationship between changes in the KP and cancer serum proteins using SPSS. RESULTS:We found that the KP was elevated in BrCa patients with local and distant metastasis compared to healthy controls and stage 1 BrCa patients. The activity of kynurenine monooxygenase (KMO) and kynureninase (KYNU) A was positively associated with disease stage and was higher compared to healthy controls. Proteome analysis in patients with local or distant metastasis revealed the dysregulation of 14 proteins, 9 of which were up-regulated and 5 down-regulated at the distant metastasis stage. Importantly, three of these proteins have not been previously linked to BrCa metastasis. In the correlation studies between the KP profile, cancer serum proteins and metastasis status, KYNU A had the greatest number of significant associations with cancer serum protein, followed by KMO. CONCLUSION:Our findings reveal that the KP was regulated differently at various stages of BrCa and was more dysregulated in patients with local or distant metastasis. These KP activity changes showed a significant association with cancer serum proteins in BrCa patients with local or distant metastasis, highlighting the potential role of KP in BrCa metastasis.

ABSTRACTLongitudinal studies that continuously generate data enable the capture of temporal variations in experimentally observed parameters, facilitating the interpretation of results in a time-aware manner. We propose IL-VIS (Incrementally Learned Visualizer), a new machine learning pipeline that incrementally learns and visualizes a progression trajectory representing the longitudinal changes in longitudinal studies. At each sampling time point in an experiment, IL-VIS generates a snapshot of the longitudinal process on the data observed thus far, a new feature that is beyond the reach of classical static models. We first verify the utility and correctness of IL-VIS using simulated data, for which the true progression trajectories are known. We find that it accurately captures and visualizes the trends and (dis)similarities between high-dimensional progression trajectories. We then apply IL-VIS to longitudinal Multi-Electrode Array data from brain cortical organoids when exposed to different levels of Quinolinic Acid, a metabolite contributing to many neuroinflammatory diseases including Alzheimer’s disease, and its blocking antibody. We uncover valuable insights into the organoids’ electrophysiological maturation and response patterns over time under these conditions.

Purpose - The phenomenon of social withdrawal, known as the hikikomori-like idiom of distress (HLID), has been reported in many countries. This study aimed to explore profiles of Omanis who have HLID. Design/methodology/approach - A cross-sectional online survey of 673 out of 1,529 Omanis identified with HLID using the Hikikomori Questionnaire (HQ-25) score of 42+. Findings - Two profile groups were determined through cluster analysis according to sociodemographic and HQ-25 outcomes. Subjects in cluster 1 (n = 168, 24.9%) are significantly younger (p < 0.001) and more educated (p = 0.019), spend more time online (p < 0.001) and are living alone (p < 0.001) than subjects in cluster 2 (n = 505, 75.1%). More subjects in cluster 1 had a past mental illness (p = 0.037) but less previous childhood physical/emotional abuse (p = 0.029) than subjects in cluster 2. In contrast, subjects in cluster 2 had a low lack of socialization (p < 0.001), less active isolation (p < 0.001) and total HQ-25 scores (p < 0.001) than cluster 1. Subjects in Cluster 1 have more serious social withdrawal issues than those in Cluster 2, especially on a lack of socialization and isolation. Research limitations/implications - One limitation that might influence the results of this online study was that information was collected via self-report, and a cross-sectional design limits its results because it cannot assess causal inference. This study has contributed valuably to exploring different profile groups of HDLD, especially in the Arabian Gulf. The authors' findings facilitate the development by creating innovative interventions strategically tackling different hikikomori groups. Originality/value - While social withdrawal characterized by HLID has been reported proliferating in different parts of the world, little research has been forthcoming from Arabian Gulf countries. These findings suggest that there are two orthogonal clusters of HLID among Omanis. This study provides a foundation for further research on HLID, which has recently been reported in different parts of the world.

The wide application of diesel engines globally and the resulting exhaust emissions have been the driving force behind producing eco-friendly alternatives to fossil diesel. Biodiesel derived from triglycerides is a promising replacement for fossil diesel due to less contribution to greenhouse gases and other harmful emissions. Transesterification is a widely adopted production method for converting triglycerides into alkyl esters, primarily owing to its superior conversion efficiency. Both homogeneous and heterogeneous catalysts, as well as enzymes, can be utilized to catalyze this process. However, commonly used catalysts often exhibit significant technical, economic, and environmental challenges, which can compromise the sustainability aspects of biodiesel production. Consequently, efforts are being directed towards developing sustainable catalysts in alignment with the United Nations Sustainable Development Goals. Among the proposed solutions, the application of nanomaterials has emerged as a promising avenue to address the limitations of conventional catalysts in the transesterification reaction. Compared with conventional catalysts, nanocatalysts have a substantially higher surface-to-volume ratio, amplifying the catalytic activity and eliminating many intrinsic limitations. In addition to their increased surface-to-volume ratio, nanocatalysts provide enhanced activity, stability, and reusability, along with greater resistance to saponification. Moreover, nanomaterials can enhance lipid extraction from feedstocks, especially from third-generation resources, due to the lack of toxicity and, subsequently, less environmental concern. While achieving promising outcomes, advancing nanotechnology as an environmentally friendly and economical approach to processing feedstocks and biodiesel production necessitates continued scrutiny. This issue is due to the potential for nanomaterials to infiltrate living systems, giving rise to various safety concerns. Thus, this review summarizes the opportunities and limitations of the mainstream applications of nanotechnology in biodiesel research.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon‐γ (IFN‐γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.

Colorectal cancer (CRC) poses a significant threat to many human lives worldwide and survival following resection is predominantly stage dependent. For early-stage cancer, patients are not routinely advised to undergo additional post-operative adjuvant chemotherapy. Acceptable clinical management guidelines are well established for patients in pTNM stages I, III and IV. However, recommendations for managing CRC stage II patients remain controversial and many studies have been conducted to segregate stage II patients into low- and high-risk of recurrence using genomic, transcriptomic and proteomic molecular markers. As proteins provide valuable insights into cellular functions and disease state and have a relatively easy translation to the clinic, this review aims to discuss potential prognostic protein biomarkers proposed for predicting tumour relapse in early-stage II CRC. It is suggested that a panel of markers may be more effective than a single marker and further evaluation is required to translate these into clinical practice.

Background Glioblastoma (GB) is a lethal and aggressive brain tumour. While molecular characteristics of GB is studied extensively, the aetiology of GB remains uncertain. The interest in exploring viruses as a potential contributor to the development of GB stems from the notion that viruses are known to play a key role in pathogenesis of other human cancers such as cervical cancer. Nevertheless, the role of viruses in GB remains controversial. Methods This review delves into the current body of knowledge surrounding the presence of viruses in GB as well as provide updates on clinical trials examining the potential inclusion of antiviral therapies as part of the standard of care protocol. Conclusions The review summarises current evidences and important gaps in our knowledge related to the presence of viruses in GB.

The utilization of renewable fuel alternatives holds promise for reducing the financial burden of regulatory compliance and the social responsibility associated with greenhouse gas emissions. Hydrothermal liquefaction (HTL) is one of the most versatile technologies for converting renewable biomass feedstocks (especially in the wet state) into biofuel (biocrude oil) in a compact plant. Therefore, this review is devoted to thoroughly reviewing and critically discussing biocrude oil production from biomass feedstocks through the HTL process. This review starts by discussing the principles of biomass HTL processing and product upgrading, aiming to provide a grounded and broad understanding of current developments in this domain. The data reported in the published literature are analyzed and visualized in order to scrutinize the effects of the main process parameters on the quantity, quality, cost, and environmental impacts of resultant biofuels. Higher biocrude oil yields are obtained at temperatures, pressures, and residual times between 300 and 350 degrees C, 24-27 MPa, and 15-25 min, respectively. Concerning yield and calorific value, biocrude oil derived from homogeneous catalysts demon-strates figures of 23.6 % and 32.1 MJ/kg, whereas that from heterogeneous catalysts exhibits percentages of 66.8 % and 40 MJ/kg, respectively. The challenges and prospects for the future development of biocrude oil are also discussed. HTL has a long way to go before being used for biofuel production on a large scale. Future studies appear to be directed towards the use of HTL technology under the biorefinery framework to maximize the exploitation of biomass into value-added products, while minimizing waste generation.

BACKGROUND:HE is a neuropsychiatric complication of liver disease characterized by systemic elevation in ammonia and proinflammatory cytokines. These neurotoxins cross the blood-brain barrier and cause neuroinflammation, which can activate the kynurenine pathway (KP). This results in dysregulated production of neuroactive KP metabolites, such as quinolinic acid, which is known to cause astrocyte and neuronal death. Our aim was to compare KP activity between patients with covert HE (CHE), patients without encephalopathic cirrhosis (NHE), and healthy controls (HCs). METHODS:This was a single-center prospective cohort study conducted between 2018 and 2021 at St Vincent's Hospital, Sydney. Overall, 13 patients with CHE, 10 patients with NHE, and 12 with HC were recruited. Patients with cirrhosis were diagnosed with CHE if they scored ≤-4 on the Psychometric Hepatic Encephalopathy Score. KP metabolite levels were quantified on plasma samples via HPLC and gas chromatography/mass spectrometry. One-way Kruskal-Wallis test was used to compare the expression levels of KP enzymes. RESULTS:KP was highly activated in patients with cirrhosis, demonstrated by higher levels of activity in the rate-limiting enzymes, indoleamine 2,3-dioxygenase, and tryptophan-2,3-dioxygenase in both CHE (65.04±20.72, p=0.003) and patients with NHE (64.85±22.10, p=0.015) compared to HC (40.95±7.301). Higher quinolinic acid concentrations were demonstrated in CHE (3726 nM±3385, p<0.001) and patients with NHE (1788 nM±632.3, p=0.032) compared to HC (624 nM±457). KP activation was positively correlated with inflammatory marker C-reactive protein in patients with CHE (Rs=0.721, p≤0.01). CONCLUSIONS:KP is highly activated in patients with CHE, resulting in heightened production of neurotoxic metabolites. Dysregulation of the pathway is demonstrable in patients who do not yet show clinical signs of neurocognitive impairment. Therapeutic agents that modulate KP activity may be able to alleviate symptoms of patients with CHE.

Abstract Glioblastoma (GB), a grade IV brain cancer, has the lowest survival rate. Despite aggressive and targeted therapies, patients remain to have the worst prognosis. More than 16% of cancer incidence worldwide has been attributed to infectious agents, raising uncertainties about the role of infections in the development of brain cancer. While numerous studies have suggested potential viral involvement in GB pathogenesis, a common limitation is the reliance on a singular technology, such as DNA/RNA sequencing or immunohistochemistry, within each study. This approach may restrict the comprehensive exploration of viral contributions, as different technologies offer distinct insights into the complex mechanisms underlying GB development. Utilizing a combination of techniques could provide a more holistic understanding, enhancing the robustness of findings and potentially uncovering nuanced aspects of viral influence that a single technology might overlook. To clarify the role of viruses in GB pathology, our study employs a comprehensive approach integrating three distinct research methods. We screened 178 publicly accessible raw mass spectrometry (MS) data of GB tumors from three independent publications (PMID: 31331834, 31154438, 36720864) by employing our internally developed data identification pipeline. The pipeline transforms raw MS data for downstream analysis, conducts database searches against the latest viral protein databases and undergoes peptide validation for enhanced robustness. Subsequent analysis filters duplicate hits and consolidates nested peptides. The final protein list includes only those identified with two or more peptides of over eight amino acids. The pipeline concludes by inferring and listing the corresponding viruses, ensuring a comprehensive and refined approach to the identification and analysis of viral proteins in the context of MS data. To enhance this dataset, we incorporated whole-genome metagenomics and MS-based proteomics, examining a preliminary cohort of15 GB tumor tissues. This approach explored a wide range of viral encoded proteins. Our comprehensive analysis, integrating bioinformatics, genomics, and proteomics, identified multiple herpesvirus species across our cohorts. This potential identification of viruses within GB has the capacity to redefine the stratification of tumor types in GB patients, signaling a significant development in our understanding of the disease. Citation Format: Bavani Gunasegaran, Aziz Abdullah A Alnakli, Gilles J. Guillemin4, Seong Beom Ahn, Benjamin Heng. Leveraging multi omics approach to examine the potential role of causative viruses in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 788.

Background: Recent advancements in understanding plasma extracellular vesicles (EVs) and their role in disease biology have provided additional unique insights into the study of Colorectal Cancer (CRC). Methods: This study aimed to gain biological insights into disease progression from plasma-derived extracellular vesicle proteomic profiles of 80 patients (20 from each CRC stage I-IV) against 20 healthy age- and sex-matched controls using a high-resolution SWATH-MS proteomics with a reproducible centrifugation method to isolate plasma EVs. Results: We applied the High-Stringency Human Proteome Project (HPP) guidelines for SWATH-MS analysis, which refined our initial EV protein identification from 1362 proteins (10,993 peptides) to a more reliable and confident subset of 853 proteins (6231 peptides). In early-stage CRC, we identified 11 plasma EV proteins with differential expression between patients and healthy controls (three up-regulated and eight down-regulated), many of which are involved in key cancer hallmarks. Additionally, within the same cohort, we analysed EV proteins associated with tumour recurrence to identify potential prognostic indicators for CRC. A subset of up-regulated proteins associated with extracellular vesicle formation (GDI1, NSF, and TMED9) and the down-regulation of TSG101 suggest that micro-metastasis may have occurred earlier than previously anticipated. Discussion: By employing stringent proteomic analysis and a robust SWATH-MS approach, we identified dysregulated EV proteins that potentially indicate early-stage CRC and predict recurrence risk, including proteins involved in metabolism, cytoskeletal remodelling, and immune response. While our findings underline discrepancies with other studies due to differing isolation and stringency parameters, they provide valuable insights into the complexity of the EV proteome, emphasising the need for standardised protocols and larger, well-controlled studies to validate potential biomarkers.

Air pollutants are increasingly emitted into the atmosphere because of the high dependency of humans on fossil-derived fuels. Wind speed and direction assisted high dispersibility and uncontrolled nature of air pollution across geo-/demographical borders, making it one of the major global concerns. Besides climate change, air pollution has been found to be associated with various diseases, such as cancer. Lung cancer, which is the world's most common type of cancer, has been found to be associated with traffic-related air pollution. Research and political efforts have been taken to explore green/renewable energy sources. However, these efforts at the current intensity cannot cope with the increasing need for fossil fuels. More specifically, political tensions such as the Russian-Ukraine war, economic tension (e.g., China-USA economic tensions), and other issues (e.g., pandemic, higher inflation rate, and poverty) significantly hindered phasing out fossil fuels. In this context, an increasing global population will be exposed to traffic-related air pollution, which justifies the current uptrend in the number of lung cancer patients. To combat this health burden, novel treatments with higher efficiency and specificity must be designed. One of the potential "life changer" options is microRNA (miRNA)-based therapy to target the expression of oncogenic genes. That said, this review discusses the association of traffic-related air pollution with lung cancer, the changes in indigenous miRNAs in the body during lung cancer, and the current status of miRNA therapeutics for lung cancer treatment. We believe that the article will significantly appeal to a broad readership of oncologists, environmentalists, and those who work in the field of (bio)energy. It may also gain the policymakers' attention to establish better health policies and regulations about air pollution, for example, by promoting (bio)fuel exploration, production, and consumption.

Sonic Hedgehog (Shh) signaling plays a critical role during central nervous system (CNS) development, and its dysregulation leads to neurological disorders. Nevertheless, little is known about Shh signaling regulation in the adult brain. Here, we investigated the contribution of DNA methylation on the transcriptional control of Shh signaling pathway members and its basal distribution impact on the brain, as well as its modulation by inflammation. The methylation status of the promoter regions of these members and the transcriptional profile of DNA-modifying enzymes (DNA Methyltransferases - DNMTs and Tet Methylcytosine Dioxygenase - TETs) were investigated in a murine model of neuroinflammation by qPCR. We showed that, in the adult brain, methylation in the CpG promoter regions of the Shh signaling pathway members was critical to determine the endogenous differential transcriptional pattern observed between distinct brain regions. We also found that neuroinflammation differentially modulates gene expression of DNA-modifying enzymes. This study reveals the basal transcriptional profile of DNMTs and TETs enzymes in the CNS and demonstrates the effect of neuroinflammation on the transcriptional control of members of the Shh Signaling pathway in the adult brain.

Sustainable socio-economic development largely depends on the sustainability of the energy supply from economic, environmental, and public health perspectives. Fossil fuel combustion only meets the first element of this equation and is hence rendered unsustainable. Biofuels are advantageous from a public health perspective, but their environmental and economic sustainability might be questioned considering the conflicts surrounding their feedstocks, including land use change and fuel vs. food conflict. Therefore, it is imperative to put more effort into addressing the downsides of biofuel production using advanced technologies, such as nanotechnology. In light of that, this review strives to scrutinize the latest developments in the application of nanotechnology in producing biodiesel, a promising alternative to fossil diesel with proven environmental and health benefits. The main focus is placed on nanotechnology applications in the feedstock production stage. First, the latest findings concerning the application of nanomaterials as nanofertilizers and nanopesticides to improve the performance of oil crops are presented and critically discussed. Then, the most promising results reported recently on applying nanotechnology to boost biomass and oil production by microalgae and facilitating microalgae harvesting are reviewed and mechanistically explained. Finally, the promises held by nanomaterials to enhance animal fat production in livestock, poultry, and aquaculture systems are elaborated. Despite the favorable features of using nanotechnology in biodiesel feedstock production, the presence of nanoparticles in living systems is also associated with important health and environmental challenges, which are critically covered and discussed in this work.