搜索结果：Lesser-Known

The pursuit of natural therapeutic drugs has fuelled interest in metabolomics, particularly marine metabolomics, with sea cucumbers standing out for their high nutritional value and potential for bioactive metabolites. However, limited research, especially in Southern Africa, has resulted in significant knowledge gaps regarding the value of lesser-known species, contributing to the exploitation of select high-value species due to rising market demand for holothurian products. This study aimed to address these gaps by characterising the metabolic profile of three body tissue extracts-body wall, gonad, and gut/mesentery-from Thyone aurea, an endemic species found along the Western Coast of Southern Africa, using untargeted 1H NMR metabolomics and full-scan UPLC-QTOF-MS/MS. The results revealed a diverse array of amino acids, sugars, and organic acids, with the gut/mesentery tissue and spring-summer extracts exhibiting the highest potential for variable metabolites. However, these patterns represent relative signatures requiring further validation with fresh tissues. While some compounds may be integral to sea cucumber physiology, the origin of others remains unclear, warranting further research into holothurian metabolic pathways and the potential impact of dietary sources and microbial activity on the metabolome. Therefore, this study emphasises the importance of expanding research to understand the metabolic responses to environmental changes, which could offer valuable insights to support conservation and sustainable cultivation strategies. Moreover, these findings underscore the need to explore lesser-known species as alternative resources in cultivation strategies to promote sustainable holothurian resources for commercial, pharmaceutical, and nutritional applications. Overall, this research enhances our understanding of sea cucumber biology and underscores the importance of incorporating a broader range of species in scientific research.

Morphogenesis, growth, shape, mechanics, and transparency of the ocular lens critically depend on cytoskeletal networks and cell adhesive interactions. However, the molecular composition of these cellular components of lens fibers remains to be defined in depth. This study is aimed at providing an unbiased and comprehensive characterization of cytoskeletal and cytoskeleton-associated proteins in human lens fibers. Transparent lenses from young adult human donors (ages 21 and 31), with capsules removed, were processed to enrich the cytoskeletome fraction, which was then trypsin-digested and subjected to proteomics analysis using a Q Exactive HF Orbitrap LC-MS/MS spectrometer. Selected proteins were validated by immunoblotting and immunofluorescence. Gene Ontology enrichment analysis was performed to classify the identified proteins. Proteomic analysis identified 530 proteins in the human lens fiber cytoskeletome, including known and lesser-known cytoskeletal, membrane-associated, adhesive, scaffolding, signaling, and metabolic proteins. Notably, several neuron preferred proteins, chaperonins, and proteasome, signaling, and redox regulators were enriched in the cytoskeletal interactome. Many of the neuron preferred proteins were localized to the cortical lens fiber cells. In addition, certain cytoskeletal protein profiles differed between human and mouse lenses. This study provides the first comprehensive profile of the human lens fiber cytoskeletome. It highlights the presence of neuron-enriched cytoskeletal, adhesive, and scaffolding proteins; cytoskeletal chaperonins; proteasome, signaling, and redox regulators; and both canonical and lesser-known cytoskeletal proteins. These findings suggest that a diverse, complex, and dynamically regulated cytoskeletal network contributes to lens fiber cell architecture, adhesion, trafficking, mechanics, and clarity.

Kratom (Mitragyna speciosa) contains over 50 alkaloids, yet the pharmacological activity of most remains poorly defined, limiting our understanding of its therapeutic potential and safety profile. We conducted a comprehensive evaluation of both indole and oxindole alkaloids at human mu-, kappa-, and delta-opioid receptors (hMOR, hKOR, hDOR), integrating radioligand binding, cAMP inhibition, β-arrestin2 recruitment, [35S]GTPƔS assays, and molecular docking. While the activity of major alkaloids like mitragynine and 7-hydroxymitragynine is well documented, we report detailed functional and structural characterization of lesser-known kratom alkaloids, including epiallo-isopaynantheine, isopaynantheine, mitraciliatine, and isospeciofoline. These compounds exhibited diverse receptor selectivity and functional profiles, ranging from G protein-biased agonism to mixed MOR antagonism/KOR agonism. Notably, speciophylline demonstrated positive allosteric modulation at hMOR without direct orthosteric binding - a mechanism not previously demonstrated experimentally for kratom alkaloids at human opioid receptors. Several oxindole alkaloids showed potent hMOR agonism with minimal β-arrestin2 recruitment, representing an extreme G-protein signaling bias that distinguishes them from classical opioids. Structure-activity analysis identified conserved pharmacophoric elements at C15 and C20 that govern receptor affinity and functional profile across both indole and oxindole scaffolds. This systematic characterization at human opioid receptors reveals a pharmacologically diverse and structurally tunable class of natural products with potential as templates for developing opioid analgesics with improved therapeutic profiles.

Cardiovascular disease has been the leading cause of death in the United States since 1921 and remains a substantial cause of morbidity and mortality worldwide. Since the discovery of statins, significant improvements in outcomes have been achieved as these drugs have direct atherogenic lipid lowering properties as well as pleiotropic effects on atherosclerotic cardiovascular disease (ASCVD). In recent years, the American Heart Association and the American College of Cardiology published a 10-year ASCVD event risk calculator to standardized risk assessment and guide statin therapy. Over the last quarter century statins have become a cornerstone of primary and secondary ASCVD management. Our review explores the evolution of statin therapy from early groundbreaking trials to shaping current ASCVD guidelines. We investigate the mechanism of action of statins, their lesser-known side effects, and their impact on other lipid particles, coronary artery calcium scoring, and C-reactive protein levels. We examine how the current understanding of ASCVD risk factors and risk enhancers provides new insights to guide indeterminate treatment decisions in individuals with intermediate ASCVD risk profiles. Additionally, we explore the evolving landscape of ASCVD therapy as new targets like proprotein convertase subtilisin/kexin 9, Lp(a), and specific inflammatory markers have garnered interest. Our comprehensive review provides an in-depth discussion of statins and novel therapies in their clinical applications for healthcare providers in the management of ASCVD.

Public health resources are often allocated based on reported disease cases. However, for under-recognized infectious diseases such as tick-borne viruses, risk assessments should also account for ecological and socioeconomic factors that influence disease case reporting. This study identifies country-level predictors of tick-borne virus reporting and evaluates whether wealthier nations are more likely to report resource-intensive cases. We applied boosted regression trees, a robust machine learning algorithm, to a comprehensive global database of tick-borne viruses and 24 environmental and socioeconomic variables. Countries with lower income inequality and greater expertise in verterinary, agricultural, or forestry sectors are more likely to report tick-borne virus cases. Wealthier nations with stronger institutional and professional capacity exhibit higher reporting rates, whereas countries affected by conflict or limited health infrastructure show underreporting. Climatic factors, particularly subartic environments, also contribute to reporting likelihood, complementing the effects of socioeconomic drivers. Disease reporting is shaped by both ecological context and socioeconomic capacity. Strengthening surveillance through targeted resource allocation and better integration of veterinary and public health expertise under the One Health framework could enhance global tick-borne disease mitigation. These findings provide valuable evidence to support the World Health Organization's Global Arbovirus Initiative and emphasize the need for equitable disease surveillance across regions. Public health resources are often allocated based on reported disease cases, but for lesser-known diseases like tick-borne viruses, reported cases may not match areas where the risk is highest. Detecting and reporting these diseases requires both individual awareness and institutional support, which may be limited in under-resourced countries. We examine how environmental and socioeconomic factors influence where tick-borne viruses are reported worldwide. Using regression-based machine learning algorithms, we find that both ecological and socioeconomic factors matter, and wealthier nations are more likely to report overlooked diseases. Integrating veterinary and public health expertise under a One Health approach, that recognizes the interconnectedness of human, animal, and environmental health, will strengthen disease surveillance and promote healthier communities.

Pollinator assemblages of different habitats are widely studied, but sampling methodologies and covering of lesser-known pollinators and other flower-visitor taxa (e.g., floriphagous species) need improvement to obtain reliable data on the structure and functioning of these communities. We assessed flower-visiting insect assemblages in arable lands and apple orchards of the eastern Pannonian Lowland using phenylacetaldehyde-based volatile traps originally developed for pest monitoring. In seven sites, 27,539 individuals belonging to 123 species and seven insect orders were recorded. On average, over 90% of the captured insects were potential pollinators, with a higher proportion in orchards (98%) than in arable lands (85%). In orchards, the dominant groups were Hymenoptera, Diptera, Lepidoptera and Neuroptera, while in arable lands, Lepidoptera were most abundant. Floriphagous and pest species were more numerous in arable lands. These results demonstrate that phenylacetaldehyde-baited traps are easy to use, standardized, and sufficiently efficient for assessing of flower-visiting assemblages. Beyond their application in pest monitoring, they can provide reliable data on the flower-visiting and pollinator assemblages in different natural and agricultural habitats.

Robust species richness estimates are critical for meaningful conservation prioritisation, understanding ecosystem resilience, and studying evolutionary processes. Yet, they remain elusive even for some of the best-studied groups and regions. As keystone pollinators, bees are crucial for the maintenance of healthy ecosystems, yet rigorous estimates of their species richness are lacking. Here, we statistically estimate global, continental, and country lower bounds of bee species richness. Globally, we estimate 24,705-26,164 bee species, an 18-25% increase, representing at least 32-45 years of taxonomic research. We estimate particularly high undescribed biodiversity from Asia, Africa, and the Americas. We find that taxonomic gaps are correlated with gross domestic product per capita (GDPc), observed species richness, number of occurrence records, and completeness of occurrence databases. Our statistical R-package framework will progress our understanding of lesser-known groups, downstream consensus, and mobilise existing occurrence datasets to quantitatively estimate species richness on global scales.

Multiple myeloma (MM) is a plasma cell neoplasm. Studies of chemokines in MM pathogenesis have primarily focused on CCR1 ligands such as CCL3 (MIP-1α), CXCL12 and its receptor CXCR4, as well as CXCR2 and CXCR3 ligands. However, the roles of the remaining 30 chemokines have been investigated much less frequently. This review compiles current knowledge on the significance of lesser-known chemokines in MM tumor processes, including CXCL13, CCR2 ligands (CCL2 [MCP-1], CCL7 [MCP-3]), CCL4, CCL5 (RANTES), CCL17, CCL20, CCL27, CCL28, and CX3CL1 (fractalkine). It describes their impact on bone destruction, bone marrow angiogenesis, chemoresistance, and the recruitment of cells into the MM niche, such as macrophages, myeloid-derived suppressor cells, and cytotoxic lymphocytes, along with their effects on mesenchymal stromal cells. A bioinformatic analysis highlights the significance of these chemokines in MM, and the possibility of targeting them in MM therapy is also considered.

Flowering marks a pivotal transition in a plant's life cycle, signalling the shift from vegetative growth to reproductive development. Over the years, extensive research has uncovered key genes and regulatory networks governing this process. Central to this regulation is the Florigen Activation Complex (FAC), along with its interacting partners and upstream and downstream components, which have been well-characterized across numerous plant species. More recently, attention has turned to a lesser-known gene, FLOWERING PROMOTING FACTOR 1 (FPF1). Initially identified in Arabidopsis thaliana, FPF1 is a plant-specific gene lacking known functional domains, yet it plays a conserved and critical role in floral induction across diverse species. Despite its discovery in 1997, the molecular mechanism of FPF1 remained elusive until recent studies began to unravel the function of FPF and its homologs. One such study revealed that FPF1-Like Protein 1 (FLP1) in Arabidopsis is expressed in phloem companion cells sites of FLOWERING LOCUS T (FT) production. Like AtFT, AtFLP1 acts as a mobile florigenic signal, though it operates independently of the canonical AtFT pathway. AtFLP1 promotes flowering by activating the floral homeotic gene SEP3, suggesting an alternative regulatory route also influenced by photoperiod. Interestingly, studies in Brachypodium distachyon have highlighted a contrasting role for FLP-like genes, where they negatively regulate flowering by interfering with the FAC, underscoring species-specific diversity in its function. While initial studies have been majorly focused on their role in flowering, in recent years FPF1 family genes have also been implicated in other developmental processes, including stem and root elongation and shade avoidance responses. In this review, we explore these emerging insights into FPF1-like proteins, examining their multifaceted roles in flowering regulation and broader developmental functions, with a special emphasis on the most recent and impactful studies.

Pharmacy technicians are well known and respected for their invaluable contributions to patient care in pharmacy settings. Pharmacy technicians have skills in practical medication information, medication access, insurance and cost navigation, and patient and provider communication strategies. In the current healthcare landscape, costly prescription medications save lives, but insurance complexities, patient social determinants of health, and other system factors create barriers. A lesser-known area of practice where pharmacy technicians significantly impact patients is primary care. Primary care pharmacy technicians (PCPhT) improve timely patient access to medications through cost mitigation and formulary navigation, provide support in the medication procurement process, and educate patients and providers on best practices to get patients the medications they need in an efficient, cost-effective manner. This commentary articulates the rationale for establishing this role, along with the PCPhT designation, as an emerging and important member of the primary care team.

Sex disparities in depression and its treatment are well-documented, but less is known about how these patterns vary across the lifespan and intersect with race, neighborhood vulnerability, and prior health challenges. We analyzed data from 2.5 million patients sampled from the Epic Cosmos Electronic Health Record (EHR) database. Active antidepressant prescriptions were used as a proxy for depression diagnoses. Data were stratified by age, sex, race/ethnicity, residence, Social Vulnerability Index (SVI 2018), prior antidepressant use, and high-risk behaviors (HIV and chlamydia testing). Rates of prescriptions by sex and odds ratios (OR) for females versus males across age at time of visit were calculated. The probability of receiving an antidepressant prescription rose sharply during adolescence, but more steeply for females, with female vs. male differences peaking at ages 17-18 (OR = 2). In the overall population, the sex gap narrowed in young adulthood (OR = 1.6 at ages 25-30), remained stable through mid-life, and widened again after age 55 (OR = 1.75 by age 70). However, the later-life increase was not observed uniformly across some groups, such as the unmarried, divorced, and living in vulnerable areas. The white population had noticeably higher prescription rates across the life span, while the Asian group had the highest adolescent peak (female vs. male OR = 2.75). Prior HIV and chlamydia testing strata demonstrated higher antidepressant prescribing and a larger, earlier adolescent female-to-male OR, although this factor likely explains only a small portion of the overall adolescent sex difference at the population level. The well-known depression sex gap in adolescents observed in the general population, and the lesser-known retirement gap, are shaped by a combination of demographic, economic, and behavioral factors, explored in this study.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by a mutation to the dystrophin gene. Cognitive dysfunction is a lesser-known symptom of DMD; however, approximately one-third of patients experience it. Though the mechanisms underlying these dysfunctions are unknown, research points towards an Alzheimer's disease (AD)-like pathology in clinical and preclinical work. In a recent study, we previously demonstrated that inhibiting glycogen synthase kinase 3 (GSK3) through a combination of low-dose lithium supplementation and voluntary wheel running (VWR) improved muscle quality and function in the mdx mouse model of DMD. Interestingly, both VWR and GSK3 inhibition with lithium can exert neuroprotective effects against Alzheimer's pathology; however, whether this treatment can also benefit cognitive function in mdx mice remains unknown. Here, we conducted a brief follow-up study to determine whether inhibiting GSK3 with a combination of low-dose lithium supplementation and VWR would enhance novel object recognition in mdx mice, while also investigating potential mechanisms, including beta-secretase activity, Tau phosphorylation, and sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Our findings show that lithium and VWR treatment, on average, improved novel object recognition in mdx mice-a result that may be linked to enhanced SERCA activity within the hippocampus but not to any changes in beta-secretase activity or tau phosphorylation. Taken together, these data point to the potential benefits of Li and VWR on cognitive function in mdx mice, highlighting the need for future research aimed at teasing out the potential mechanisms.

This comprehensive review explores the properties and applications of natural oils derived from diverse animal sources. Fish-based supplements are today widely consumed for their nutritional/health benefits. In this context, this review opens doors to lesser-known oils that can be explored for such properties. Focusing on the nutritional spectra of omega-3 and omega-6 essential fatty acids, the document highlights the well-established benefits of fish oil, particularly for cardiovascular health. Further, little-known animalderived oils, including emu, crocodile, ostrich, cobra, and krill oils, are being studied for their unique chemical compositions and potential health benefits. These oils exhibit wound-healing (for burns and diabetic wounds), anti-inflammatory, anti-arthritic, and antimicrobial activities, and are used in the treatment of chemotherapy- induced mucositis and hyperlipidemia. Attempts are also made to understand the mechanistic pathways and signal modulations that contribute to the beneficial properties of these oils. Presently, the effective utilization of these oils in the mainstream is limited and underutilized. As our dependence on plant-based products increases, questioning their sustainability, lesser-known natural oils obtained through the processing of waste animal fats can be effectively employed, harnessing newer alternatives in nutrition, medicine, and therapeutics.

Ruthenium, a critical metal, plays an increasingly important role in modern applications, such as catalysts for chemical synthesis and the production of hard disk drives. As a result, the supply has struggled to meet the growing demand in recent years. The economic position of ruthenium presents an opportunity to examine the methods of its extraction, particularly given that it is a lesser-known platinum group metal. This article explores the concentration of ruthenium in natural sources and the methods used in primary production, with a particular focus on hydrometallurgical techniques applied at an industrial scale. It also discusses secondary ruthenium-containing materials, including spent catalysts, metallurgical by-products, wastewaters, spent nuclear fuel. The article provides a detailed analysis of the composition of these materials, emphasizing hydrometallurgical methods like leaching and separation processes, along with the recovery of final products.

Immune checkpoint inhibitor immunotherapy enhances T cell activity against cancer cells but often leads to the immune system targeting healthy cells, causing 'immune-related adverse events' (irAEs). We report the case of a man in his 70s with metastatic melanoma being treated with ipilimumab and nivolumab. He presented with febrile neutropenia after lacerating a thumb on his compost bin. The neutrophil count only recovered once oral prednisolone was commenced, indicating a haematological irAE. A restaging Positron Emission Tomography scan revealed intramuscular ring-enhancing collections throughout his body, one of which was aspirated and cultured the fungus Lomentospora prolificans He was treated with voriconazole plus terbinafine, both of which were later substituted with olorofim due to a voriconazole-induced rash. After 4 months, the collections had resolved on repeat imaging, and olorofim was ceased due to transaminitis. This case highlights neutropenia as a lesser-known adverse effect of immunotherapy and raises awareness about L. prolificans infection.

Category learning-the ability to group individual objects, experiences, and concepts into higher-level abstract representations-is fundamental to fast, flexible decision-making and generalization of knowledge to novel situations. While categories and concepts have traditionally been studied in humans and nonhuman primates, this review puts the focus on the lesser-known domain of rodent category learning. Within the context of human and nonhuman primate work, we highlight the behavioral capabilities and limitations of rodents in categorization tasks, and discuss the neural circuits identified so far. Finally, we outline a roadmap for uncovering the systems and synaptic mechanisms that support the representation of learned categories in the mammalian brain.

Nitric oxide is a short-lived gas that plays a critical role in numerous physiological processes, including vascular regulation, neurotransmission, and immune responses. In the CNS NO's role is complex, as it can both protect and damage neurons. Microglia, the brain's resident macrophages, produce excessive NO in response to stimuli like endotoxins and cytokines, leading to chronic inflammation and neuronal damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. NO's dual role as a pro-inflammatory and anti-inflammatory mediator is intricately linked to its impact on neuronal health and disease progression. This review is aimed at summarizing and critically discussing the roles of NO in neuroinflammation, neurodegeneration, inflammasome regulation, and related therapeutic perspectives. A narrative literature review was conducted using electronic databases (e.g. PubMed and Google Scholar) to identify experimental and clinical studies on NO, neuroinflammation, neurodegenerative diseases, inflammasomes, and related biomarkers and therapies, with emphasis on mechanistic and translational work. Research into NO's effects on inflammasomes, key components of the innate immune system, reveals that NO can inhibit inflammasome activation, influencing inflammatory responses. Despite progress, challenges remain, including the need for cell-type-specific models, advanced technological approaches, and the development of selective NO modulators. Overall, current evidence indicates that NO exerts both neuroprotective and neurotoxic effects in the CNS, mediated by its complex interactions with neural, glial, and immune pathways. Future research should focus on the dual nature of NO, explore lesser-known inflammasomes, and incorporate human-centric models to develop targeted therapies.

Biosynthetic gene clusters (BGC) are genomic regions that encode the production of specialized metabolites, including antibiotics, pigments, and toxins. While BGC are traditionally classified into broad categories such as NRPS, PKS, and terpene clusters, these classes often overlook finer relationships among gene clusters that produce structurally or functionally related compounds. Tools like BiG-SCAPE and BiG-SLiCE have been developed to address this issue by organizing BGC into gene cluster families (GCFs). CORASON complements these tools by enabling phylogenetic reconstruction of BGC, identifying conserved core genes, and visualizing GFCs as a continuum of variation in gene presence/absence and sequence identity. Although CORASON is incorporated in BiG-SCAPE visualization, it is also a standalone tool initially designed for bacterial genomes annotated via RAST and implemented through Docker in Linux environments. Here, we demonstrate CORASON's broader applicability using fungal GenBank files and its installation via Conda on Windows. As a case study, we examine metagenome-assembled genomes (MAGs) from Fusarium domesticum, a lesser-known member of the Fusarium genus, which is often present in food-associated microbiomes. Unlike its pathogenic relatives (F. oxysporum, F. graminearum), F. domesticum remains understudied, making it an interesting target for genomic mining. This work expands the accessibility of CORASON for fungal genome analysis and highlights its potential in uncovering novel biosynthetic potential in overlooked microbial taxa.