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The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer's disease (AD) and further emphasizes the significance of neuroinflammatory pathways in regulating Aβ accumulation. Indeed, Aβ accumulation triggers microglia activation, which are key mediators in neuroinflammation. The inflammatory responses in this process can lead to neuronal damage and functional decline. Microglia secrete proinflammatory cytokines that accelerate neuronal death and release anti-inflammatory cytokines and growth factors contributing to neuronal recovery and protection. Thus, microglia play a dual role in neurodegeneration and neuroprotection, complicating their function in AD. Therefore, elucidating the complex interactions between Aβ protein, microglia, and neuroinflammation is essential for developing new strategies for treating AD. This review investigates the receptors and pathways involved in activating microglia and aims to enhance understanding of how these processes impact neuroinflammation in AD, as well as how they can be regulated. This review also analyzed studies reported in the existing literature and ongoing clinical trials. Overall, these studies will contribute to understanding the regulatory mechanisms of neuroinflammation and developing new therapies that can slow the pathological progression of AD. [ABSTRACT FROM AUTHOR]

The domestication and breeding of wheat genotypes through the years has led to the loss in their genetic variation, making them more prone to different abiotic stresses. Boron (B) toxicity is one of the stresses decreasing the wheat cultivars' yield in arid and semi-arid regions around the world. Wild wheat progenitors, such as Triticum urartu Thumanian ex Gandilyan, possess a broader gene pool that harbors several genes conferring tolerance to various biotic and abiotic stresses. Unfortunately, T. urartu is not well-explored at the molecular level for its tolerance towards B toxicity in soil. In this study, for the first time, we compared the transcriptomic changes in the leaves of a high B-tolerant T. urartu genotype, PI662222, grown in highly toxic B (10 mM B in the form of boric acid) with the ones grown in the control (3.1 μM B) treatment in hydroponic conditions. The obtained results suggest that several mechanisms are involved in regulating the response of the studied T. urartu genotype toward B toxicity. All the growth parameters of T. urartu genotype, including root–shoot length, root fresh weight, and root–shoot dry weight, were less affected by high boron (10 mM) as compared to the boron-tolerant bread wheat cultivar. With a significant differential expression of 654 genes, 441 and 213 genes of T. urartu genotype were down- and upregulated, respectively, in the PI662222 leaves in high B in comparison to the control treatment. While key upregulated genes included those encoding RNA polymerase beta subunit (chloroplast), ATP synthase subunit gamma, chloroplastic, 60S ribosomal protein, and RNA-binding protein 12-like, the main downregulated genes included those encoding photosystem II protein D, ribulose bisphosphate carboxylase small subunit, and peroxidase 2-like. Interestingly, both Gene Ontology enrichment and KEGG pathways emphasized the possible involvement of the genes related to the photosynthetic process and apparatus in the high B tolerance of the T. urartu genotype. The further functional characterization of the identified potential T. urartu genes will facilitate their utilization in crop improvement programs for B toxicity stress. [ABSTRACT FROM AUTHOR]

In this work, combined efforts by Greek and Turkish scientists produced an updated validated NIS inventory of the Aegean ecoregion, covering 120 years of records up to August 2024. Of the 342 NIS currently present in the Aegean Sea, the majority (281 species) have invaded the South Aegean, followed by the North Aegean (128 species out of 206 NIS). A total of 73 species were added to the list, while 56 were removed. Overall, unaided spread of Lessepsian immigrants from the Levantine Sea and shipping are equally responsible for NIS reported at the regional level. An increase in publications addressing NIS matches the upward trend of NIS since the mid-1990s, which continues to the present day. While unaided introductions of Lessepsian species and/or direct introductions via the Suez Canal peaked in the South Aegean during 2000–2005, they peaked in 2012–2017 in the North Aegean—a decade later. The opposite pattern was observed in ship-transferred NIS. The spatial distribution of introduction hotspots largely reflects the following phenomena/processes: unaided introduction is witnessed initially in the southeastern Aegean Sea; monitoring efforts are concentrated in vulnerable and at-risk areas; and research efforts relate to the spatial allocation of institutions and marine experts working on marine NIS along the Aegean coasts. [ABSTRACT FROM AUTHOR]

Tea production and quality are largely determined by the many genetic and biochemical characteristics that occur in tea plant cultivars. Worldwide, tea is consumed for its pleasing and refreshing effects due to its caffeine content. The present study performed transcriptomics analyses of two tea species (Camellia sinensis var. Shuchazao (SCZ) and Camellia ptilophylla (CAF)) and identified diversity in the gene expression levels and major regulatory transcription factors (TFs) for the characterization of purine alkaloids and phenylpropanoid biosynthesis pathways. The RNA-seq analysis of two species (SCZ and CAF) revealed the differences in caffeine and catechins synthesis. In the purine alkaloid biosynthesis pathway, the S-adenosyl methionine (SAM) and adenosine monophosphate (AMP) pathway genes were significantly related to xanthosine synthesis in contrasting purine alkaloids among (Camellia sinensis var. Shuchazao (SCZ) and Camellia ptilophylla (CAF)). The significant expression of SAMS-5, PPAT-2, IMPDH-2, TCS-2, TCS-3, XMT-1, XMT-13, and XDH-4 in the xanthosine degradation pathway in CAF is attributed to higher theobromine content as compared to SCZ. Moreover, the transcription factors (TFs) AP2/ERF (20%), WRKY (12%), NAC (11%), and MYB (8%) were significantly correlated. The upregulated expression of caffeine synthesis genes in SCZ was correlated with MYB and AP2/ERF transcription factors. This study provides the basis for differences in the genetic mechanism in purine alkaloids, phenylpropanoid, and flavonoid biosynthesis pathways, which would be helpful in the development and selection of tea plant species with high or low caffeine concentrations. This study also provides a road map for future genetic improvement in tea species and cultivars. [ABSTRACT FROM AUTHOR]

Arsenic is a common toxic heavy metal contaminant that is widely present in the ocean, and seaweeds have a strong ability to concentrate arsenic, posing a potential risk to human health. This study first analyzed the arsenic content in two different seaweeds and then used an innovative method to categorize the seaweeds into low-arsenic and high-arsenic groups based on their arsenic exposure levels. Finally, a non-targeted metabolomic analysis based on mass spectrometry was conducted on seaweed from different arsenic exposure groups. The results indicated that as the arsenic concentration increased in the seaweeds, linolenic acid, tyrosine, pheophorbide a, riboflavin, and phenylalanine were upregulated, while arachidonic acid, eicosapentaenoic acid (EPA), betaine, and oleamide were downregulated. The following four key metabolic pathways involving unsaturated fatty acids and amino acids were identified: isoquinoline alkaloid biosynthesis, tyrosine metabolism, phenylalanine metabolism, and riboflavin metabolism. The identification of biomarkers and the characterization of key metabolic pathways will aid in the selection and breeding of low-arsenic-accumulating seaweed varieties, providing insights into the metabolic and detoxification mechanisms of arsenic in seaweeds. [ABSTRACT FROM AUTHOR]

Simple Summary: This article explores the molecular pathways involved in lung cancer, alongside genomic alterations and genetic syndromes associated with the disease. It also reviews testing methods and their role in advancing personalized treatment approaches, offering insights into current therapeutic strategies. This article provides a comprehensive overview of lung cancer from a genetic perspective, emphasizing the molecular pathways involved in its pathogenesis. This review presents the genetic syndromes and key genomic variations, including alterations and instabilities, contributing to tumor development and progression. Furthermore, advancements in genomic testing, such as liquid biopsy, are explored, highlighting their utility in early diagnosis, prognostic evaluation, and personalized treatment strategies. The role of biomarkers in informing therapeutic decisions and optimizing patient outcomes is also examined, offering insights into their potential to refine clinical interventions. This review aims to enrich the understanding of the genetic landscape of lung cancer, providing insights that may lead to improved diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: High-grade serous ovarian cancer (HGSC) has a high heterogeneity both among patients and within a single tumor. Four molecular subtypes of HGSC were previously described. These studies were based on analysis of several types of microarrays. Then, classifiers were created based on these results to determine the molecular subtype. When developing these classifiers, the application to high-throughput sequencing data, especially single-cell data, was not considered. In this paper, we created OVsignGenes, a neural network model for determining the HGSC subtype that can process bulk RNA-Seq or single-cell RNA-Seq data, including spatial transcriptomic data. Background/Objectives: High-grade serous carcinomas (HGSCs) are highly heterogeneous tumors, both among patients and within a single tumor. Differences in molecular mechanisms significantly describe this heterogeneity. Four molecular subtypes have been previously described by the Cancer Genome Atlas Consortium: differentiated, immunoreactive, mesenchymal, and proliferative. These subtypes may have varying degrees of progression, relapse-free survival, and overall survival, as well as response to therapy. The precise determination of these subtypes is certainly necessary both for diagnosis and future development of targeted therapies within personalized medicine. Methods: In this study, we analyzed gene expression data based on bulk RNA-seq, scRNA-seq, and spatial transcriptomic data from six cohorts (totaling 535 samples, including 60 single-cell samples). Differential expression analysis was performed using the edgeR package. The KEGG database and GSVA package were used for pathways enrichment analysis. As a predictive model, a deep neural network was created using the keras and tensorflow libraries. Results: We identified 357 differentially expressed genes among the four subtypes: 96 differentiated, 33 immunoreactive, 91 mesenchymal, and 137 proliferative. Based on these, we created OVsignGenes, a neural network model resistant to the effects of platform (test dataset AUC = 0.969). We then ran data from five more cohorts through our model, including scRNA-seq and spatial transcriptomics. Conclusions: Because the differentiated subtype is located at the intersection of the other three subtypes based on PCA and does not have a unique profile of differentially expressed genes or enriched pathways, it can be considered an initiating subtype of tumor that will develop into one of the three other subtypes. [ABSTRACT FROM AUTHOR]

Seed germination is crucial for plant survival, crop stand establishment, and achieving optimal grain yield. The main objective of this review is to explore the physiological and molecular mechanisms governing rice seed germination under aerobic (water stress) and anaerobic (hypoxic) conditions in direct-seeded rice (DSR) systems. Moreover, it discusses the recent genomic advancements and innovations to improve rice seed germination. Here, we discuss how coleoptile and mesocotyl elongation plays a vital role in anaerobic germination (AG) and the function of raised antioxidants, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in maintaining Reactive Oxygen Species (ROS), and malondialdehyde (MDA) homeostasis for stabilizing seed germination in water-scarce conditions. This study comprehensively highlights the functions and dynamics of phytohormones—GA (gibberellic acid) and ABA (abscisic acid)—key regulatory genes, transcription factors (TFs), key proteins, and regulatory metabolic pathways, including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA), in regulating seed germination under both conditions. Conventional agronomic and cultural practices, such as seed selection, seed priming, seed coating, and hardening, have proven to improve seed germination. Moreover, the utilization of molecular and novel approaches—such as clustered regularly interspaced short palindromic repeat (CRISPR-Cas9) mediated genome editing, marker-assisted selection (MAS), genome-wide associations studies (GWAS), single nucleotide polymorphisms (SNPs), multi-omics, RNA sequencing—combined with beneficial quantitative trait loci (QTLs) has expanded knowledge of crop genomics and inheritance. These advancements aid the development of specific traits for enhancing seed germination in DSR. [ABSTRACT FROM AUTHOR]

A checklist of Lesvos Island's non-native vascular flora is presented. Through the literature and a roadside survey, we recorded 187 non-native plant taxa, representing 12% of the total regional flora. A total of 37 taxa were reported for the first time for Lesvos, including three taxa that are also new to the Greek non-native flora. The dominant families were Fabaceae, Asteraceae, Poaceae, Amaranthaceae, and Solanaceae. Amaranthus, Oxalis, Solanum, Opuntia, and Prunus were the most species rich genera. Most taxa were neophytes, naturalized and perennial, while phanerophytes and therophytes were the predominant life forms. Animal (insect) pollination was the principal pollination mode, whereas the main dispersal mechanism was zoochory, with most taxa forming a capsule. The majority of the taxa preferred agricultural and ruderal habitats and originated from the Americas and Asia. The primary introduction pathway was escape from confinement, concerning taxa introduced for ornamental and agricultural purposes. [ABSTRACT FROM AUTHOR]

Adenomyosis is a benign gynecological condition characterized by the proliferation of the endometrial stroma and glands into the myometrium, uterine volume enlargement, and peripheral smooth muscle hypertrophy. The typical clinical symptoms include chronic pelvic pain, abnormal uterine bleeding, and subfertility, all of which significantly impact quality of life. There are no effective prevention or treatment strategies for adenomyosis, partly due to a limited understanding of the pathological mechanisms underlying the initiation and progression of the disease. Given that signaling pathways play a crucial role in the development of adenomyosis, a better understanding of these signaling pathways is essential for identifying therapeutic targets and advancing drug development. The occurrence and progression of adenomyosis are closely linked to various underlying pathophysiological mechanisms, including proliferation, migration, invasion, fibrosis, angiogenesis, inflammation, oxidative stress, immune response, and epigenetic changes. This review summarizes the signaling pathways and targets associated with the pathogenesis of adenomyosis, including CXCL/CXCR, NLRP3, NF-κB, TGF-β/smad, VEGF, Hippo/YAP, PI3K/Akt/mTOR, JAK/STAT, and other relevant pathways. In addition, it identifies promising future targets for the development of adenomyosis treatment, such as m6A, GSK3β, sphks, etc. [ABSTRACT FROM AUTHOR]

Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways. [ABSTRACT FROM AUTHOR]

The complex and multidimensional effect of climate change, coupled with low socioeconomic development, in Sub-Saharan Africa (SSA) makes the region vulnerable to the changing climate and threatens its inhabitants' survival, livelihood, and health. Subnational actions have been widely acclaimed as effective in combatting climate change. Local governments in SSA have been developing and implementing climate action plans to reduce greenhouse gas (GHG) emissions. In this article, we qualitatively assessed climate change mitigation technical pathways at the city level by studying four major African megacities' climate plans and actions. The cities studied are Accra, Ghana; Addis Ababa, Ethiopia; Lagos, Nigeria; and Nairobi, Kenya. This study provides insight into the novel and innovative policy design and instrumentation options to sustainably address climate change mitigation in SSA. With the past literature focusing on climate adaptation for the Global South, this study shows leading context-specific efforts in climate change mitigation that simultaneously address local sustainable development needs. Our assessment identified the prioritized technical pathways for climate change mitigation in the selected cities, as well as innovative techniques and areas for improvement. Given that it also identifies emerging best practices, this study's findings can be helpful to local governments and practitioners pursuing local deep decarbonization and international organizations supporting these programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Ulva prolifera is an important species with a large market value. This species thrives at 10–20 °C but struggles at lower temperatures. Research has demonstrated that environmental stresses, such as temperature and light intensity, have a substantial impact on its growth through changing pathways and gene expression. Our present study examines the processes by which U. prolifera responds to combined high light intensity/temperature challenges, and the results point to the involvement of several genes and pathways in these intricate adaptive mechanisms. Gaining an understanding of these systems is essential to enhancing the efficiency and sustainability of macroalgae farming, particularly in light of climate change. Our research focused on understanding the genetic mechanisms that contribute to the tolerance of Ulva prolifera (Chlorophyta), a marine macroalgae, to the combined stress of high temperature and high light intensity. At the mRNA level, the up-regulated DEGs showed enrichment in pathways related to ribosomes, proteasomes, and peroxisomes. The spliceosome pathway genes were found to be vital for U. prolifera's ability to adapt to various challenging situations in all the comparison groups. In response to elevated temperature and light intensity stress, there was a significant increase in genes and pathways related to ribosomes, proteasomes, and peroxisomes, whereas autophagy showed an increase in response to stress after 24 h, but not after 48 h. These findings provide novel insights into how U. prolifera adapts to elevated temperature and light stress. [ABSTRACT FROM AUTHOR]

Metabolism is a 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 the 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-validation 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 was 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. [ABSTRACT FROM AUTHOR]

Head and neck cancer ranks as the sixth-most common malignancy worldwide, characterized by high mortality and recurrence rates. Research studies indicate that molecular diagnostics play a crucial role in the early detection and prognostic evaluation of these diseases. This study aimed to identify potential biomarkers for head and neck cancer and elucidate their interactions with miRNAs and possible therapeutic drugs. Four drivers, namely, FN1, IL1A, COL1A1, and MMP9, were identified using network biology and machine learning approaches. Gene set variation analysis (GSVA) showed that these genes were significantly involved in different biological processes and pathways, including coagulation, UV-response-down, apoptosis, NOTCH signaling, Wnt-beta catenin, and other signal pathways. The diagnostic value of these hub genes was validated using receiver operating characteristic (ROC) curves. The top interactive miRNAs, including miR-128-3p, miR-218-5p, miR-214-3p, miR-124-3p, miR-129-2-3p, and miR-1-3p, targeted the key genes. Furthermore, the interaction between the key genes and drugs was also identified. In summary, the key genes and miRNAs or drugs reported in this study might provide valuable information for potential biomarkers to increase the prognosis and diagnosis of head and neck cancer. [ABSTRACT FROM AUTHOR]

Carbon peaking and carbon neutrality strategies bring both opportunities and challenges to the development of green buildings. In this context, the development of high-quality green buildings requires a focus on improving carbon reduction effects throughout their entire lifespan. Based on a systematic review of the achievements and existing problems in the development of green buildings in China over the past thirty years, this article benchmarks the new trends in green building standards in developed countries abroad, dissects the new requirements for the development of green buildings in China under the new situation, and proposes a high-quality carbon reduction pathways from four aspects: theoretical research, policy systems, technical systems, and software platforms. Finally, it proposes implementation suggestions for collaborative development from four dimensions: theoretical methods for calculating carbon emissions, green finance policies, a full-process carbon reduction technology system, and carbon emission accounting tools. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field. It is largely unknown whether epigenetic modifications interfere with DOAC response or whether DOAC treatment induces epigenetic modifications. To fill this gap, we started the miR-CRAFT (Circulating microRNAs and DNA methylation as regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation) research study. In miR-CRAFT, we follow, over time, changes in DNA methylation and microRNAs expression in naïve AF patients starting DOAC treatment. The ultimate goal of miR-CRAFT is to identify the molecular pathways epigenetically affected by DOACs, beyond the coagulation cascade, that are potentially mediating DOAC pleiotropic actions and to propose specific microRNAs as novel circulating biomarkers for DOAC therapy monitoring. We herein describe the study design and briefly present the progress in participant enrolment. [ABSTRACT FROM AUTHOR]

Youth homelessness presents a complex and persistent challenge worldwide, particularly affecting young adults between 16 and 24 years of age in the US and Canada. This population faces elevated risks of exploitation, victimization, and various health issues upon detachment from familial support structures. Understanding the multi-faceted nature of youth homelessness requires the consideration of individual, structural, and systemic factors within the socio-ecological model. Historically, when examining youth homelessness, traditional methods have concentrated either on individual factors contributing to homelessness or on broader structural issues within society. The emergence of the new orthodoxy attempted to bridge the apparent gap between individual- and structural-level factors by considering both to be equally significant, but it faced skepticism for its theoretical framework. In response, the "pathways" approach gained traction, emphasizing the subjective experiences and agency of youth experiencing homelessness. Departing from conventional epidemiological models, the pathways approach views homelessness as a dynamic process intertwined with individual life contexts. This paper navigates the scholarly discourse on youth homelessness and examines the distinct characteristics of the pathways approach. By exploring its implications for research and policy, this study contributes to a nuanced understanding of youth homelessness and informs future prevention-focused interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Epigenetic factor microRNAs may modulate vaccine protective efficacy well, supported by experimental data showing that the expression of some microRNAs drastically differs between well-protected and poorly protected genetic lines of chickens. Marek's disease vaccination and virus challenge trials were conducted in two genetically divergent inbred lines of chickens, and hundreds of microRNAs were identified. However, a small number of miRNAs were observed with significant differential expression per line per vaccination treatment group. One of the vaccines was HVT, which reportedly protects the two lines of birds with a significant difference. The target genes of the differentially expressed miRNAs in response to HVT were reportedly involved with many Gene Ontology terms and pathways, which suggests there is a high complexity of the genetic/epigenetic mechanism modulating vaccine protective efficacy. Epigenetic factors, including microRNAs (miRNAs), play an important role in affecting gene expression and, therefore, are involved in various biological processes including immunity protection against tumors. Marek's disease (MD) is a highly contagious disease of chickens caused by the MD virus (MDV). MD has been primarily controlled by vaccinations. MD vaccine efficacy might, in part, be dependent on modulations of a complex set of factors including host epigenetic factors. This study was designed to identify differentially expressed miRNAs in the primary lymphoid organ, bursae of Fabricius, in response to MD vaccination followed by MDV challenge in two genetically divergent inbred lines of White Leghorns. Small RNA sequencing and bioinformatic analyses of the small RNA sequence reads identified hundreds of miRNAs among all the treatment groups. A small portion of the identified miRNAs was differentially expressed within each of the four treatment groups, which were HVT or CVI988/Rispens vaccinated line 63-resistant birds and line 72-susceptible birds. A direct comparison between the resistant line 63 and susceptible line 72 groups vaccinated with HVT followed by MDV challenge identified five differentially expressed miRNAs. Gene Ontology analysis of the target genes of those five miRNAs revealed that those target genes, in addition to various GO terms, are involved in multiple signaling pathways including MAPK, TGF-β, ErbB, and EGFR1 signaling pathways. The general functions of those pathways reportedly play important roles in oncogenesis, anti-cancer immunity, cancer cell migration, and metastatic progression. Therefore, it is highly likely that those miRNAs may, in part, influence vaccine protection through the pathways. [ABSTRACT FROM AUTHOR]

The aim of this article is to suggest a better—theoretically and empirically grounded—understanding of the complex character of social justice in higher education. Theoretically, this article conceptualises social justice in higher education as mediating participation in, completion of and outcomes from higher education. It introduces the concept of composite capability for achieving higher education that captures capabilities to participate in, complete and gain outcomes from higher education. This study also develops a methodology for building an empirically based classification of countries regarding social justice in participation in higher education, taking into account the assessed inequality in students' pathways to higher education as well as inequality in their social conditions, associated with students' social origin. In so doing, it develops three indices: the index of inequalities in students' pathways, the index of inequalities in students' social conditions and the index of participation in higher education. Using microdata from the EUROSTUDENT VII survey (2019–2021) for 12 European countries, it applies the developed methodology to classify countries, for which data are available, by the degree of fairness in participation in higher education. This study's results demonstrate the social embeddedness of social justice in higher education in different economic and political contexts. [ABSTRACT FROM AUTHOR]

Preserving the dwindling native biodiversity in urban settings poses escalating challenges due to the confinement of remaining natural areas to isolated and diminutive patches. Remarkably scarce research has scrutinised the involvement of institutions, particularly universities, in introducing alien plant species in South Africa, thus creating a significant gap in effective monitoring and management. In this study, the Tshwane University of Technology in Tshwane Metropole, South Africa serves as a focal point, where we conducted a comprehensive survey of alien plants both within the university premises and beyond its confines. The investigation involved the classification of invasion status and a meticulous assessment of donor and recipient dynamics. Our findings encompass 876 occurrence records, revealing the presence of 94 alien plant species spanning 44 distinct families. Noteworthy occurrences among the dominant plant families are Asteraceae and Solanaceae. Herbaceous and woody plants emerged as the most prevalent alien species, with common representation across both sampling sites. A substantial majority of recorded species were initially introduced for horticultural purposes (51%) before escaping and establishing self-sustaining populations (62%). Furthermore, 43 species identified are listed in South African invasive species legislation, with some manifesting invasive tendencies and altering the distribution of native species in the remaining natural areas. The notable overlap in species observed between the university premises and adjacent areas provides crucial insights into the influence of institutions on the dynamics of plant invasions within the urban landscape. This underscores the prevailing gaps in the management of invasive alien plants in urban zones and accentuates the imperative of an integrated approach involving collaboration between municipalities and diverse institutions for effective invasive species management in urban environments. [ABSTRACT FROM AUTHOR]

The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <−0.5 (p < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options. [ABSTRACT FROM AUTHOR]

Over time, the renowned Kyoto Encyclopedia of Genes and Genomes (KEGG) has grown to become one of the most comprehensive online databases for biological procedures. The majority of the data are stored in the form of pathways, which are graphs that depict the relationships between the diverse items participating in biological procedures, such as genes and chemical compounds. However, the size, complexity, and diversity of these graphs make them difficult to explore and understand, as well as making it difficult to extract a clear conclusion regarding their most important components. In this regard, we present KEGGSum, a system enabling the efficient and effective summarization of KEGG pathways. KEGGSum receives a KEGG identifier (Kid) as an input, connects to the KEGG database, downloads a specialized form of the pathway, and determines the most important nodes in the graph. To identify the most important nodes in the KEGG graphs, we explore multiple centrality measures that have been proposed for generic graphs, showing their applicability to KEGG graphs as well. Then, we link the selected nodes in order to produce a summary graph out of the initial KEGG graph. Finally, our system visualizes the generated summary, enabling an understanding of the most important parts of the initial graph. We experimentally evaluate our system, and we show its advantages and benefits. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Krüppel-like Factor-9 (KLF9) and Krüppel-like Factor-13 (KLF13) are highly related proteins that function as inducers and/or repressors of specific target gene repertoires in a variety of tissues and in diverse pathophysiological states, including neoplasia. Here, we describe the salient features of KLF9 and KLF13, the current state-of-the-art research regarding both protein's actions in cancer development and response to therapies, and where the field requires further exploration. These paralogous proteins warrant further study for multiple cancers, and with respect to their multiplicities of action in suppression or promotion of proliferative and metastatic phenotypes, and likely involvement in immune cell biology within the tumor microenvironment. Specificity Proteins/Krüppel-like Factors (SP/KLF family) are a conserved family of transcriptional regulators. These proteins share three highly conserved, contiguous zinc fingers in their carboxy-terminus, requisite for binding to cis elements in DNA. Each SP/KLF protein has unique primary sequence within its amino-terminal and carboxy-terminal regions, and it is these regions which interact with co-activators, co-repressors, and chromatin-modifying proteins to support the transcriptional activation and repression of target genes. Krüppel-like Factor 9 (KLF9) and Krüppel-like Factor 13 (KLF13) are two of the smallest members of the SP/KLF family, are paralogous, emerged early in metazoan evolution, and are highly conserved. Paradoxically, while most similar in primary sequence, KLF9 and KLF13 display many distinct roles in target cells. In this article, we summarize the work that has identified the roles of KLF9 (and to a lesser degree KLF13) in tumor suppression or promotion via unique effects on differentiation, pro- and anti-inflammatory pathways, oxidative stress, and tumor immune cell infiltration. We also highlight the great diversity of miRNAs, lncRNAs, and circular RNAs which provide mechanisms for the ubiquitous tumor-specific suppression of KLF9 mRNA and protein. Elucidation of KLF9 and KLF13 in cancer biology is likely to provide new inroads to the understanding of oncogenesis and its prevention and treatments. [ABSTRACT FROM AUTHOR]

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing and to properly classify all ovarian cancers. In this article, we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels, details about the genes, and also candidate genes. We hope to bring new information to the medical field so as to better prevent and diagnose ovarian cancer. [ABSTRACT FROM AUTHOR]

Chronic stress is known to perturb serotonergic regulation in the brain, leading to mood, learning and memory impairments and increasing the risk of developing mood disorders. The influence of the gut microbiota on serotonergic regulation in the brain has received increased attention recently, justifying the investigation of the role of diet on the gut and the brain in mood disorders. Here, using a 4-week chronic unpredictable mild stress (CUMS) model in mice, we aimed to investigate the effects of a high-fat high-glycaemic index (HFD) and high-fibre fruit & vegetable "superfood" (SUP) modifications of a semi-pure AIN93M diet on behaviour, serotonin synthesis and metabolism pathway regulation in the brain and the gut, as well as the gut microbiota and the peripheral adrenal medullary system. CUMS induced anxiety-like behaviour, dysregulated the tryptophan and serotonin metabolic pathways in the hippocampus, prefrontal cortex, and colon, and altered the composition of the gut microbiota. CUMS reduced the catecholamine synthetic capacity of the adrenal glands. Differential effects were found in these parameters in the HFD and SUP diet. Thus, dietary modifications may profoundly affect the multiple dynamic systems involved in mood disorders. [ABSTRACT FROM AUTHOR]

Conjunctival melanoma (CM) is a rare but aggressive cancer. Over the past decade, molecular studies using rapidly advancing technologies have increasingly improved our understanding of CM genetics. CMs are mainly characterized by dysregulated MAPK and PI3K/AKT/mTOR pathways, driven by commonly mutated (BRAF, NRAS, NF1) or less commonly mutated (KIT, PTEN) genes. Another group of genes frequently mutated in CMs include TERT and ATRX, with known roles in telomere maintenance and chromatin remodeling/epigenetic regulation. Uveal melanoma-related genes (BAP1, SF3B1, GNAQ/11) can also be mutated in CMs, albeit infrequently. Additional CM-related mutated genes have increasingly been identified using more comprehensive genetic analyses, awaiting further confirmation in additional/larger studies. As a tumor arising in a partly sun-exposed mucosal tissue, CM exhibits a distinct genomic profile, including the frequent presence of an ultraviolet (UV) signature (and high mutational load) and also the common occurrence of large structural variations (distributed across the genome) in addition to specific gene mutations. The knowledge gained from CM genetic studies to date has led to new therapeutic avenues, including the use of targeted and/or immuno-therapies with promising outcomes in several cases. Accordingly, the implementation of tumor genetic testing into the routine clinical care of CM patients holds promise to further improve and personalize their treatments. Likewise, a growing knowledge of poor prognosis-associated genetic changes in CMs (NRAS, TERT, and uveal melanoma signature mutations and chromosome 10q deletions) may ultimately guide future strategies for prognostic testing to further improve clinical outcomes (by tailoring surveillance and considering prophylactic treatments in patients with high-risk primary tumors). [ABSTRACT FROM AUTHOR]

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associated with the FMR1 premutation. Currently, it is not possible to determine when and if individual premutation carriers will develop FXTAS. Thus, with the aim to identify biomarkers for early diagnosis, development, and progression of FXTAS, along with associated dysregulated pathways, we performed blood proteomic profiling of premutation carriers (PM) who, as part of an ongoing longitudinal study, emerged into two distinct groups: those who developed symptoms of FXTAS (converters, CON) over time (at subsequent visits) and those who did not (non-converters, NCON). We compared these groups to age-matched healthy controls (HC). We assessed CGG repeat allele size by Southern blot and PCR analysis. The proteomic profile was obtained by liquid chromatography mass spectrometry (LC-MS/MS). We identified several significantly differentiated proteins between HC and the PM groups at Visit 1 (V1), Visit 2 (V2), and between the visits. We further reported the dysregulated protein pathways, including sphingolipid and amino acid metabolism. Our findings are in agreement with previous studies showing that pathways involved in mitochondrial bioenergetics, as observed in other neurodegenerative disorders, are significantly altered and appear to contribute to the development of FXTAS. Lastly, we compared the blood proteome of the PM who developed FXTAS over time with the CSF proteome of the FXTAS patients recently reported and found eight significantly differentially expressed proteins in common. To our knowledge, this is the first report of longitudinal proteomic profiling and the identification of unique biomarkers and dysregulated protein pathways in FXTAS. [ABSTRACT FROM AUTHOR]

In numerous environmental compartments around the world, the existence of micro- and nanoplastics (MNPs) in the environment has been verified. A growing number of studies have looked at the interaction between MNPs and human activities due to the risks they may pose to humans. Exposure pathways are key factors in measuring MNPs risks. However, current research largely ignores the contribution of mechanical fragmentation pathways to MNPs exposure during the daily use of plastic products. Our critical review demonstrated the research gap between MNP fragmentation and risk assessments via a network analysis. The release of fragmented MNPs and their properties were also described at various scales, with emphasis on environmental stressors and mechanical fragmentation. In the scenarios of daily use, plastic products such as food packaging and clothing provide acute pathways of MNPs exposure. The release tendency of those products (up to 102 mg MNPs) are several orders of magnitude higher than MNPs abundances in natural compartments. Despite the limited evidence available, waste recycling, landfill and municipal activities represented long-term pathways for MNPs fragmentation and point sources of MNPs pollution in environmental media. Assessing the health effects of the fragmentation process, unfortunately, is further hampered by the current absence of human exposure impact assessments for secondary MNPs. We proposed that future studies should integrate aging evaluation into risk assessment frameworks and establish early warning signs of MNPs released from plastic products. [ABSTRACT FROM AUTHOR]

Skeletal muscle is the protein reservoir of our body and an important regulator of glucose and lipid homeostasis. The dystrophin gene is the largest gene and has a key role in skeletal muscle construction and function. Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans, mice, dogs, and cats. Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular condition causing progressive muscle weakness and premature death. β-hydroxy β-methylbutyrate (HMB) prevents deleterious muscle responses under pathological conditions, including tumor and chronic steroid therapy-related muscle losses. The use of HMB as a dietary supplement allows for increasing lean weight gain; has a positive immunostimulatory effect; is associated with decreased mortality; and attenuates sarcopenia in elderly animals and individuals. This study aimed to identify some genes, metabolic pathways, and biological processes which are common for DMD and HMB based on existing literature and then discuss the consequences of that interaction. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease of the airways characterized by shortness of breath, chest tightness, coughing, and wheezing. For several decades (approximately 30 years), miRNAs and their role in asthma have been of constant interest among scientists. These small, non-coding RNA fragments, 18–25 nucleotides long, regulate gene expression at the post-transcriptional level by binding to the target mRNA. In this way, they affect several biological processes, e.g., shaping airway structures, producing cytokines and immune mediators, and controlling defense mechanisms. Publications confirm their potential role in the diagnosis and monitoring of the disease, but only some articles address the use of miRNAs in the treatment of asthma. The following paper reviews the latest available studies and presents miRNAs as a useful tool for predicting the effectiveness of the included treatment, early diagnosis of exacerbations, and in assessing patient compliance for different groups of drugs used in asthma. The latest known pathways underlying the pathogenesis of the disease, which are associated with a change in miRNA expression, may be precise targets of therapeutic activity in the future. [ABSTRACT FROM AUTHOR]

Flavonoids are secondary metabolites that are non-essential for plant growth or survival, and they also provide numerous health benefits to humans. They are antioxidants that shield plants from the ill effects of ultraviolet light, pests, and diseases. They are beneficial to health for several reasons, including lowering inflammation, boosting cardiovascular health, and lowering cancer risk. This study looked into the physicochemical features of these substances to determine the potential pharmacological pathways involved in their protective actions. Potential targets responsible for the protective effects of quercetin, naringenin, and rutin were identified with SwissADME. The associated biological processes and protein–protein networks were analyzed by using the GeneMANIA, Metascape, and STRING servers. All the flavonoids were predicted to be orally bioavailable, with more than 90% targets as enzymes, including kinases and lyases, and with common targets such as NOS2, CASP3, CASP9, CAT, BCL2, TNF, and HMOX1. TNF was shown to be a major target in over 250 interactions. To extract the "biological meanings" from the MCODE networks' constituent parts, a GO enrichment analysis was performed on each one. The most important transcription factors in gene regulation were RELA, NFKB1, PPARG, and SP1. Treatment with quercetin, naringenin, or rutin increased the expression and interaction of the microRNAs' hsa-miR-34a-5p, hsa-miR-30b-5p, hsa-let-7a-5p, and hsa-miR-26a-1-3p. The anticancer effects of hsa-miR-34a-5p have been experimentally confirmed. It also plays a critical role in controlling other cancer-related processes such as cell proliferation, apoptosis, EMT, and metastasis. This study's findings might lead to a deeper comprehension of the mechanisms responsible for flavonoids' protective effects and could present new avenues for exploration. [ABSTRACT FROM AUTHOR]

Temperature is considered to be a major abiotic factor influencing aquatic life. Marine heatwaves are emerging as threats to sustainable shellfish aquaculture, affecting the farming of New Zealand's green-lipped mussel [Perna canaliculus (Gmelin, 1791)]. In this study, P. canaliculus were gradually exposed to high-temperature stress, mimicking a five-day marine heatwave event, to better understand the effects of heat stress on the metabolome of mussels. Following liquid chromatography-tandem mass spectrometry analyses of haemolymph samples, key sugar-based metabolites supported energy production via the glycolysis pathway and TCA cycle by 24 h and 48 h of heat stress. Anaerobic metabolism also fulfilled the role of energy production. Antioxidant molecules acted within thermally stressed mussels to mitigate oxidative stress. Purine metabolism supported tissue protection and energy replenishment. Pyrimidine metabolism supported the protection of nucleic acids and protein synthesis. Amino acids ensured balanced intracellular osmolality at 24 h and ammonia detoxification at 48 h. Altogether, this work provides evidence that P. canaliculus has the potential to adapt to heat stress up to 24 °C by regulating its energy metabolism, balancing nucleotide production, and implementing oxidative stress mechanisms over time. The data reported herein can also be used to evaluate the risks of heatwaves and improve mitigation strategies for aquaculture. [ABSTRACT FROM AUTHOR]

Currently, hydropower is the principal renewable energy source; however, climate change is increasing the frequency of extreme events, such as floods, droughts, erosion, and sedimentation of rivers, which produce uncertainty with regard to hydroelectric generation. Thus, this study aimed to analyze the climate change projections for the hydropower systems of Ecuador based on data from 14 projects studying scenarios according to the Shared Socioeconomic Pathways from the Intergovernmental Panel on Climate Change. The study examined the period from 2010 to 2020 with historical data, determined the tendency, defined a database year, and then projected the scenarios to 2050. The quantitative methodology used time-series statistics for Ecuador's hydropower inflow to calculate the deviation over recent years and develop a model to simulate future power generation. The results showed that hydropower in Ecuador is expected to decrease considerably through to 2050 due to meteorological changes. In this calculation of the Shared Socioeconomic Pathways, the selected scenarios showed a reduction in SSP5 of 11.5%, SP2 of 16.2%, and SSP4 of 18.2% through to 2050, indicating that the opportunities for hydroelectric production in the face of climate change are variable, but the challenges are broad. In Ecuador, the projections of reductions in hydropower generation represent a sensitive issue, especially knowing that, in 2020, 87% of the energy grid in the country depended on hydroelectric production. [ABSTRACT FROM AUTHOR]

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated with severe human diseases. Although the physiological function of these proteins is still elusive, their relationship with neurodegeneration and cancer has been clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules to their involvement in tumor-related processes, and discuss the putative use of these proteins as cancer molecular biomarkers. [ABSTRACT FROM AUTHOR]

Molecular heterogeneity in prostate cancer (PCa) is one of the key reasons underlying the differing likelihoods of recurrence after surgical treatment in individual patients of the same clinical category. In this study, we performed RNA-Seq profiling of 58 localized PCa and 43 locally advanced PCa tissue samples obtained as a result of radical prostatectomy on a cohort of Russian patients. Based on bioinformatics analysis, we examined features of the transcriptome profiles within the high-risk group, including within the most commonly represented molecular subtype, TMPRSS2-ERG. The most significantly affected biological processes in the samples were also identified, so that they may be further studied in the search for new potential therapeutic targets for the categories of PCa under consideration. The highest predictive potential was found with the EEF1A1P5, RPLP0P6, ZNF483, CIBAR1, HECTD2, OGN, and CLIC4 genes. We also reviewed the main transcriptome changes in the groups at intermediate risk of PCa—Gleason Score 7 (groups 2 and 3 according to the ISUP classification)—on the basis of which the LPL, MYC, and TWIST1 genes were identified as promising additional prognostic markers, the statistical significance of which was confirmed using qPCR validation. [ABSTRACT FROM AUTHOR]

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS. [ABSTRACT FROM AUTHOR]

Objective: The risk factors for postnatal depressive symptoms (PNDS) are numerous, but little is known about the protective factors or the interactions between different exposures. The present study explored the pathways between maternal, infant and parenthood vulnerabilities or risk/protective factors and PNDS at 2 months postpartum (PP) in a large sample of women from the general population. Methods: We used data from the French ELFE cohort, a nationally representative cohort of children followed-up from birth. The available information about vulnerabilities or risk/protective factors for PNDS was collected during the maternity ward stay (mother or medical records) and at 2 months PP (mother by phone). PNDS were evaluated with the Edinburgh Postnatal Depression Scale (EPDS) at 2 months. A measurement model was built based on the psychosocial model for PNDS of Milgrom and colleagues using exploratory factor analysis. The Structural Equation Model was used to investigate the pathways between vulnerability, risk/protective factors and PNDS at 2 months PP. Results: In the study sample (n = 11,583), a lack of a partner's perceived antenatal emotional support, consultation with a mental health specialist before pregnancy, family financial difficulties, prenatal psychological distress and a difficult pregnancy experience were directly associated with the severity of maternal PNDS at 2 months PP, as well as lack of perceived postnatal support. Family financial difficulties and consultation with a mental health specialist before pregnancy were also indirectly associated with the intensity of PNDS through a lack of perceived antenatal emotional support, a difficult pregnancy experience, prenatal psychological distress and a lack of perceived postnatal support. Regarding infant and parenthood characteristics, infant self-regulation difficulties, maternal difficulty in understanding infant crying and infant hospitalisation were directly associated with PNDS severity at 2 months PP, while maternal difficulty in understanding an infant's cries was also indirectly associated with infant self-regulation difficulties. Conclusions: Perinatal professional support should begin antenatally and target the couple's prenatal functioning, with particular attention to women presenting a history of psychiatric disorders, especially those of low socioeconomic status. After delivery, addressing infant and parenthood characteristics is also recommended. [ABSTRACT FROM AUTHOR]

As natural medicines in complementary and alternative medicine, edible and medicinal resources are being gradually recognized throughout the world. According to statistics from the World Health Organization, about 80% of the worldwide population has used edible and medicinal resource products to prevent and treat diseases. Polysaccharides, one of the main effective components in edible and medicinal resources, are considered ideal regulators of various biological responses due to their high effectiveness and low toxicity, and they have a wide range of possible applications for the development of functional foods for the regulation of common, frequently occurring, chronic and severe diseases. Such applications include the development of polysaccharide products for the prevention and treatment of neurodegenerative diseases that are difficult to control by a single treatment, which is of great value to the aging population. Therefore, we evaluated the potential of polysaccharides to prevent neurodegeneration by their regulation of behavioral and major pathologies, including abnormal protein aggregation and neuronal damage caused by neuronal apoptosis, autophagy, oxidative damage, neuroinflammation, unbalanced neurotransmitters, and poor synaptic plasticity. This includes multi-target and multi-pathway regulation involving the mitochondrial pathway, MAPK pathway, NF-κB pathway, Nrf2 pathway, mTOR pathway, PI3K/AKT pathway, P53/P21 pathway, and BDNF/TrkB/CREB pathway. In this paper, research into edible and medicinal resource polysaccharides for neurodegenerative diseases was reviewed in order to provide a basis for the development and application of polysaccharide health products and promote the recognition of functional products of edible and medicinal resources. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of the development of unhealthy metabolic phenotypes in obese children and adolescents remain unclear. We aimed to screen the metabolomes of individuals with the unhealthy obesity phenotype and identify the potential metabolic pathways that could regulate various metabolic profiles of obesity in Chinese adolescents. A total of 127 adolescents aged 11–18 years old from China were investigated using a cross-sectional study. The participants were classified as having metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) based on the presence/absence of metabolic abnormalities defined by metabolic syndrome (MetS) and body mass index (BMI). Serum-based metabolomic profiling using gas chromatography–mass spectrometry (GC–MS) was undertaken on 67 MHO and 60 MUO individuals. ROC analyses showed that palmitic acid, stearic acid, and phosphate could predict MUO, and that glycolic acid, alanine, 3-hydroxypropionic acid, and 2-hydroxypentanoic acid could predict MHO (all p < 0.05) from selected samples. Five metabolites predicted MUO, 12 metabolites predicted MHO in boys, and only two metabolites predicted MUO in girls. Moreover, several metabolic pathways may be relevant in distinguishing the MHO and MUO groups, including the fatty acid biosynthesis, fatty acid elongation in mitochondria, propanoate metabolism, glyoxylate and dicarboxylate metabolism, and fatty acid metabolism pathways. Similar results were observed for boys except for phenylalanine, tyrosine and tryptophan biosynthesis, which had a high impact [0.098]. The identified metabolites and pathways could be efficacious for investigating the underlying mechanisms of the development of different metabolic phenotypes in obese Chinese adolescents. [ABSTRACT FROM AUTHOR]

Lipid metabolism disorder has become an important hidden danger threatening human health, and various supplements to treat lipid metabolism disorder have been studied. Our previous studies have shown that DHA-enriched phospholipids from large yellow croaker (Larimichthys Crocea) roe (LYCRPLs) have lipid-regulating effects. To better explain the effect of LYCRPLs on lipid regulation in rats, the fecal metabolites of rats were analyzed from the level of metabolomics in this study, and GC/MS metabolomics measurements were performed to figure out the effect of LYCRPLs on fecal metabolites in rats. Compared with the control (K) group, 101 metabolites were identified in the model (M) group. There were 54, 47, and 57 metabolites in the low-dose (GA), medium-dose (GB), and high-dose (GC) groups that were significantly different from that of group M, respectively. Eighteen potential biomarkers closely related to lipid metabolism were screened after intervention with different doses of LYCRPLs on rats, which were classified into several metabolic pathways in rats, including pyrimidine metabolism, the citric acid cycle (TCA cycle), the metabolism of L-cysteine, carnitine synthesis, pantothenate and CoA biosynthesis, glycolysis, and bile secretion. L-cysteine was speculated to be a useful biomarker of LYCRPLs acting on rat fecal metabolites. Our findings indicated that LYCRPLs may regulate lipid metabolism disorders in SD rats by activating these metabolic pathways. [ABSTRACT FROM AUTHOR]

Potentially toxic elements (PTEs) are metallic chemicals with densities that are higher than that of water. Water pollution by PTEs due to the discharge of untreated pharmaceutical industrial effluents is a risk to human health and ecological integrity. The present review paper provides an overview of the threats to human health due to water contamination by PTEs such as lead, cobalt, cadmium, nickel, and arsenic originating from pharmaceutical industrial wastewater. This review reveals the associated advantages and shortcomings of the outmoded and the modern methods and the challenges involved in addressing the shortcomings. Additionally, due to the increasing amount of uncontrollable pharmaceutical effluents entering the ecosystem, this paper reviewed the management approach supported by the World Health Organization and the Environmental Protection Agency. Studies revealed that PTEs find their way into human bodies through different pathways, which include drinking water, edibles, and dermal vulnerability at intervals. This paper focuses on how pharmaceutical effluents can be handled and how regulations and strategies can be reinforced step by step. To preserve public health and the environment, a comprehensive study on the environmental evaluation of carcinogenic substances, particularly toxic elements and metalloids, should be supported and advocated. To protect living organisms and the welfare of consumers, efforts should be made to reduce the presence of potentially hazardous elements on land and water. [ABSTRACT FROM AUTHOR]

This paper reviews graph-theory-based methods that were recently developed in our group for post-processing molecular dynamics trajectories. We show that the use of algorithmic graph theory not only provides a direct and fast methodology to identify conformers sampled over time but also allows to follow the interconversions between the conformers through graphs of transitions in time. Examples of gas phase molecules and inhomogeneous aqueous solid interfaces are presented to demonstrate the power of topological 2D graphs and their versatility for post-processing molecular dynamics trajectories. An even more complex challenge is to predict 3D structures from topological 2D graphs. Our first attempts to tackle such a challenge are presented with the development of game theory and reinforcement learning methods for predicting the 3D structure of a gas-phase peptide. [ABSTRACT FROM AUTHOR]

Polysaccharide decolorization has a major effect on polysaccharide function. In the present study, the decolorization of Rehmannia glutinosa polysaccharides (RGP) is optimized using two methods—the AB-8 macroporous resin (RGP-1) method and the H2O2 (RGP-2) method. The optimal decolorization parameters for the AB-8 macroporous resin method were as follows: temperature, 50 °C; macroporous resin addition, 8.4%; decolorization duration, 64 min; and pH, 5. Under these conditions, the overall score was 65.29 ± 3.4%. The optimal decolorization conditions for the H2O2 method were as follows: temperature, 51 °C; H2O2 addition, 9.5%; decolorization duration, 2 h; and pH, 8.6. Under these conditions, the overall score was 79.29 ± 4.8%. Two pure polysaccharides (RGP-1-A and RGP-2-A) were isolated from RGP-1 and RGP-2. Subsequently, their antioxidant and anti-inflammatory effects and mechanisms were evaluated. RGP treatment activated the Nrf2/Keap1 pathway and significantly increased the activity of antioxidant enzymes (p < 0.05). It also inhibited the expression of pro-inflammatory factors and suppressed the TLR4/NF-κB pathway (p < 0.05). RGP-1-A had a significantly better protective effect than RGP-2-A, likely owing to the sulfate and uronic groups it contains. Together, the findings indicate that RGP can act as a natural agent for the prevention of oxidation and inflammation-related diseases. [ABSTRACT FROM AUTHOR]

This study characterised the sport participation patterns of 546 male youth team sport players. A retrospective questionnaire was used to identify the sport starting age (general sports and main sport) and the quantity and type of sports undertaken during the early years of development. A mixed-ANOVA and Chi-square tests were implemented. All participants started involvement in sports at the same age (~5 years) and participated in the same number of sports during their early years (1 to 2 sports). However, football players started participating mainly in team games (football, futsal) and water polo players in CGS sports (swimming). Participants reported different ages for initial participation in: (i) main sport (football players started participating earlier, around 5–6 years), (ii) onset of specialisation (football players specialised earlier, around 7 or 8 years), (iii) types of sports engaged in (football players were involved in more team games and water polo in more CGS sports), and (iv) variations in weekly training hours (water polo reported more hours of training). This study provided empirical evidence for understanding the effects of different sporting pathways on long-term athlete development. Some key incongruities between contemporary knowledge and practice are acknowledged. Further investigations should be developed by examining the trajectories in different sports, countries, genders, and cultural contexts. [ABSTRACT FROM AUTHOR]

Simple Summary: The dairy cattle industry relies heavily on artificial insemination facilitated by cryopreservation of bull semen. Cryopreservation causes a number of injuries to sperm reducing fertility and decreasing economic value. Protective extenders are media made up of a number of compounds. Most studies evaluate the impact of changing the concentration of one or two compounds at the same time. Here we use multivariate statistical methods on a large experimental dataset over twelve different compounds to identify key classes of compounds, key components of those classes, and the sensitivities of post-thaw viability on concentrations of these compounds. These statistical models and this methodology point towards improved cryopreservation protocols an improved understanding of the complex interactions among extender components. Cryo-injury reduces post-thaw semen quality. Extender components play a protective role, but existing experimental approaches do not elucidate interactions among extender components, semen samples, and post-thaw quality. To identify optimal concentrations for 12 extender ingredients, we ran 122 experiments with an I-optimal completely random design using a large dataset from our previous study. We obtained a maximum predicted total motility of 70.56% from an I-optimal design and 73.75% from a Monte Carlo simulation. Individual bull variations were significant and interacted with extenders independently. 67% of bulls reliably preferred extender formulations to reach maximum motility. Multifactor analysis suggests that some antioxidants may offer superior protection over others. Partial least squares path modeling (PLS-PM) found the highest positive loadings for glutathione in the antioxidant class, glycerol in the CPA class, and fructose in the basic compounds class. The optimal ranges for milk, water, and ethylene glycol were extremely narrow. Egg yolk, cholesterol-loaded cyclodextrin, and nerve growth factor had medium-loading impacts. PLS-PM showed that CPA, osmoregulators, and basic components were the most efficient contributors to motility, while the antioxidant and extracellular protectant classes had less efficiency. Thus, ingredients, concentrations, and interactions of extender compounds are critical to extender formulation, especially when using multiple compounds with the same function. [ABSTRACT FROM AUTHOR]

Pearl millet is a significant crop that is tolerant to abiotic stresses and is a staple food of arid regions. However, its underlying mechanisms of stress tolerance are not fully understood. Plant survival is regulated by the ability to perceive a stress signal and induce appropriate physiological changes. Here, we screened for genes regulating physiological changes such as chlorophyll content (CC) and relative water content (RWC) in response to abiotic stress by using "weighted gene coexpression network analysis" (WGCNA) and clustering changes in physiological traits, i.e., CC and RWC associated with gene expression. Genes' correlations with traits were defined in the form of modules, and different color names were used to denote a particular module. Modules are groups of genes with similar patterns of expression, which also tend to be functionally related and co-regulated. In WGCNA, the dark green module (7082 genes) showed a significant positive correlation with CC, and the black (1393 genes) module was negatively correlated with CC and RWC. Analysis of the module positively correlated with CC highlighted ribosome synthesis and plant hormone signaling as the most significant pathways. Potassium transporter 8 and monothiol glutaredoxin were reported as the topmost hub genes in the dark green module. In Clust analysis, 2987 genes were found to display a correlation with increasing CC and RWC. Furthermore, the pathway analysis of these clusters identified the ribosome and thermogenesis as positive regulators of RWC and CC, respectively. Our study provides novel insights into the molecular mechanisms regulating CC and RWC in pearl millet. [ABSTRACT FROM AUTHOR]

Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health–disease balance. Recent metabolomics and combined metabolome–microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., Faecalibacterium and phosphatidylethanolamine; and the opposite, Escherichia and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera Bacteroides were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera Clostridium, Roseburia, Blautia, and Oscillibacter in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota–liver cometabolites and its detoxification enzymes and pathways. [ABSTRACT FROM AUTHOR]

Proteomics offers vast potential for studying the molecular regulation of the human brain. Formalin fixation is a common method for preserving human tissue; however, it presents challenges for proteomic analysis. In this study, we compared the efficiency of two different protein-extraction buffers on three post-mortem, formalin-fixed human brains. Equal amounts of extracted proteins were subjected to in-gel tryptic digestion and LC-MS/MS. Protein, peptide sequence, and peptide group identifications; protein abundance; and gene ontology pathways were analyzed. Protein extraction was superior using lysis buffer containing tris(hydroxymethyl)aminomethane hydrochloride, sodium dodecyl sulfate, sodium deoxycholate, and Triton X-100 (TrisHCl, SDS, SDC, Triton X-100), which was then used for inter-regional analysis. Pre-frontal, motor, temporal, and occipital cortex tissues were analyzed by label free quantification (LFQ) proteomics, Ingenuity Pathway Analysis and PANTHERdb. Inter-regional analysis revealed differential enrichment of proteins. We found similarly activated cellular signaling pathways in different brain regions, suggesting commonalities in the molecular regulation of neuroanatomically-linked brain functions. Overall, we developed an optimized, robust, and efficient method for protein extraction from formalin-fixed human brain tissue for in-depth LFQ proteomics. We also demonstrate herein that this method is suitable for rapid and routine analysis to uncover molecular signaling pathways in the human brain. [ABSTRACT FROM AUTHOR]