Antipsychotic-induced myocarditis is a rare but potentially fatal adverse event associated with antipsychotic treatment. Trimetazidine (TMZ) and coenzyme Q10 (CoQ10) have shown potential cardioprotective effects. Thus, they may represent adjunctive therapeutic candidates for antipsychotic-induced myocarditis. However, the underlying molecular mechanisms and therapeutic relevance of this remain unclear. This study aimed to identify the potential pharmacological mechanisms and therapeutic targets of TMZ and CoQ10 in antipsychotic-induced myocarditis. Drug- and disease-associated targets were retrieved or predicted using SwissTargetPrediction, SEA, PharmMapper, Super-PRED, and GeneCards. Overlapping drug-disease targets were identified and used to construct a protein-protein interaction network and determine the core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed using DAVID. Finally, molecular docking and molecular dynamics simulations were conducted to evaluate ligand-target interactions and the stability of the selected complexes. Twenty-six overlapping TMZ-disease targets and 27 overlapping CoQ10-disease targets were identified. GO and KEGG enrichment analyses revealed that these targets were involved in multiple biological processes, cellular components, molecular functions, and signaling pathways. Thirty-nine unique drug-disease intersection targets were obtained after merging the TMZ-disease and CoQ10-disease targets and five core targets were identified: STAT3, NFKB1, HIF1A, CASP3, and MMP9. Further GO and KEGG enrichment analyses were conducted for the 39 drug-disease intersection targets. GO enrichment analysis indicated that the apoptotic process was greatly enriched, whereas KEGG analysis highlighted the PI3K/AKT signaling pathway. Molecular docking suggested that TMZ and CoQ10 could form stable interactions with the core targets, supporting their potential therapeutic relevance. The molecular dynamics simulations further supported the stability of the selected ligand-target complexes. Network pharmacology, molecular docking, and molecular dynamics simulations were used to investigate the potential pharmacological mechanisms underlying the effects of TMZ and CoQ10 in antipsychotic-induced myocarditis. The findings provide theoretical and computational evidence for future experimental studies on TMZ and CoQ10 as potential adjunctive therapeutic candidates for antipsychotic-induced myocarditis.
Interleukin-5 (IL-5) is a central regulator of eosinophil differentiation, maturation, survival, activation, and mobilization, and it contributes to eosinophil recruitment to inflamed tissues. These biological functions have made the IL-5/IL-5 receptor alpha (IL-5Rα) pathway a key therapeutic target in eosinophil-associated diseases. Four biologics currently target this pathway in clinical practice: mepolizumab, reslizumab, and depemokimab bind soluble IL-5, whereas benralizumab targets IL-5Rα and induces antibody-dependent cellular cytotoxicity. Clinical development has been successful in severe eosinophilic asthma (SEA), where targeting the IL-5/IL-5Rα pathway reduces exacerbation risk and can lower the need for long-term oral corticosteroid use. The therapeutic scope has since expanded to chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and idiopathic hypereosinophilic syndrome (iHES). Mepolizumab has shown efficacy across these eosinophilia-associated diseases, reducing asthma exacerbations, nasal polyp burden, EGPA relapse activity, HES flares, and eosinophils in peripheral blood. Mepolizumab is approved by both FDA and EMA for SEA, CRSwNP, EGPA, and HES. Reslizumab improves exacerbation rates and lung function in SEA and is approved by FDA and EMA for this indication. Benralizumab produces rapid and near-complete blood and tissue eosinophil depletion, reduces exacerbation rates and oral corticosteroid use in SEA, and has demonstrated sustained remissions and corticosteroid-sparing efficacy in EGPA; it is approved by FDA and EMA for SEA and EGPA. Depemokimab extends IL-5 inhibition through a long-acting, twice-yearly dosing strategy, reduces exacerbation rates in SEA, and improves nasal polyp burden in CRSwNP; it is approved by FDA and EMA for SEA and by EMA for CRSwNP. Safety data from randomized trials, extension studies, real-world cohorts, and meta-analyses are generally reassuring, with most adverse events being mild to moderate and no consistent major safety signal. This review synthesizes current understanding of IL-5 biology, critically evaluates the clinical trial evidence for IL-5/IL-5Ra-targeted biologics across major eosinophilia-associated diseases, and highlights remaining evidence gaps and future directions.
Pancreatic neuroendocrine tumors (pNETs) are biologically heterogeneous neoplasms with variable clinical outcomes. Current prognostic assessment relies largely on mitotic count and Ki-67 index, which may be affected by intratumoral heterogeneity and sampling bias. Additional biomarkers are therefore needed to refine risk stratification and characterize aggressive disease biology. Here, we investigated the prognostic and biological significance of Claudin-1 (CLDN1), a tight junction protein implicated in epithelial tumor progression. CLDN1 expression was assessed by immunohistochemistry in 67 surgically resected pNETs using tissue microarrays. A data-driven cutoff (H-score >50) identified a CLDN1-high subset associated with significantly shorter disease-free survival (p = 0.009) and adverse clinicopathologic features. To define the molecular programs underlying CLDN1 overexpression, we performed RNA sequencing on 22 tumors matched for key clinical variables by propensity score matching. CLDN1-high tumors showed attenuation of endocrine lineage markers and enrichment of exocrine and fetal ductal transcriptional programs. Cell-of-origin deconvolution further revealed a shift from endocrine alpha/beta-cell identity toward ductal or acinar-like states. Transcriptomic clustering demonstrated partial convergence between CLDN1-high pNETs and pancreatic ductal adenocarcinoma profiles. In addition, CLDN1-high tumors exhibited activation of epithelial-mesenchymal transition, HIPPO signaling, and immune-related pathways, together with increased stromal and immune cell infiltration. Collectively, our findings identify CLDN1 as a marker of a biologically distinct and clinically aggressive pNET subset characterized by dedifferentiation, lineage plasticity, and tumor microenvironment remodeling, supporting further evaluation of CLDN1 as a candidate prognostic biomarker and potential therapeutic target in pNETs.
Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 123 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide multiplex imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation. We also assessed insulin and glucagon secretory profiles in isolated islet preparations from pediatric donors aged 2 months to 10 years and found a temporal difference in the maturation of insulin secretion compared to glucagon secretion. This comprehensive summary of postnatal and pediatric pancreatic islet development provides a framework for future studies and for integrating emerging genetic and genomic data related to islet biology and diabetes risk.
Ischemic stroke(IS) is a globally prevalent neurological emergency, with its core pathology featuring oxidative stress-driven cascade injury induced by ischemia-reperfusion(I/R). This pathology involves the synergistic amplification of reactive oxygen species(ROS) burst, inflammation activation, and multiple types of cellular damage. Existing therapeutic approaches struggle to achieve simultaneous blocking of multiple targets. TCM, centering on the holistic concept and syndrome differentiation and treatment, exerts therapeutic effects via multiple components and pathways, which are highly compatible with the complex pathological network of IS. Accordingly, TCM has evolved into a key strategy for IS intervention. This article systematically summarizes the initiating and amplifying mechanisms of oxidative stress in the IS pathological cascade, and focuses on reviewing the multi-target intervention systems of TCM. The active components of single herbs precisely target key nodes of the cascade through mechanisms such as antioxidation, anti-inflammation, inhibition of abnormal cell death, protection of the blood-brain barrier(BBB), and metabolic microenvironment regulation. Classic TCM formulae achieve holistic blocking of the cascade loop by virtue of cross-system regulation, multi-link coverage, and clinical scenario adaptability. Novel intelligent drug delivery systems effectively address intracerebral delivery challenges and significantly enhance intervention efficacy. Meanwhile, this article highlights the current core research gaps: inadequate elaboration on the molecular mechanisms underlying the multicomponent synergistic intervention of TCM, insufficient standardization of clinical studies, and delayed translation of drug delivery systems into clinical applications. In the future, it is necessary to rely on interdisciplinary technologies such as systems biology and nanomedicine to deeply decipher the synergistic intervention mechanisms of TCM, and improve the basic-clinical medical translation system. In summary, TCM, through a synergistic blocking model supported by multicomponent empowerment, multi-targeting, and multistage intervention, offers a unique and feasible solution for breaking through the bottlenecks in the clinical treatment for IS and is expected to become a core intervention method for the integrated traditional Chinese and western medicine treatment of IS.
Using a combined RNA and small RNA sequencing approach, this study decodes the precise molecular mechanisms and microRNA-gene networks that govern early seminal root development in wheat. The findings pinpoint specific genetic and hormonal targets that can be leveraged through precision breeding to engineer climate-resilient crops with optimized root architectures. Climate change exerts immense pressure on wheat, threatening both its development and productivity. The transition from dormancy to seedling establishment is a critical yield checkpoint, where seminal roots act as the hidden architects of success. Within days of germination, roots must rapidly construct complex systems and adapt to environmental shifts. This early developmental phase determines seedling fate, yet the molecular mechanisms governing it are yet to be fully explored. Thus, in this study, we employed an integrative RNA and small RNA sequencing approach to dissect the regulatory networks governing Triticum aestivum seminal root development during the first weeks after seeding. Our work reveals that this stage requires the coordinated action of 385 genes and 12 microRNAs (miRs). Identified as differentially expressed, these molecules orchestrate cell division, metabolic reprogramming, and developmental patterning. Functional enrichment analysis showed that cell wall biosynthesis and remodeling, SNARE-mediated vesicular trafficking, terpenoid metabolism, and phytohormone signaling pathways are dynamically regulated during early root growth. Among all, miR166, miR168, and miR171 emerged as pivotal post-transcriptional regulators. These miRs exhibited expression patterns inversely correlated with their predicted targets, encoding HD-ZIP III transcription factors, spliceosomal kinases, and GRAS like family proteins, which are essential factors for vascular patterning, microRNA biogenesis, and lignin deposition, respectively. Notably, these genetic programs are synchronized with dramatic hormonal recalibration, marking the transition from dormancy to active growth. Beyond advancing our fundamental understanding of root biology, the present findings identify specific molecular targets (i.e., stage-related expressed genes and miRs) that could be manipulated through precision breeding or genome editing to develop wheat varieties with enhanced root systems resilient to environmental changes.
Despite broad consensus on the importance of genetic counseling (GC) in the era of genomic medicine, formal recognition of GC as an independent profession remains uneven worldwide. This study aimed at understanding factors that hinder its establishment in some countries and identifying the most pressing questions surrounding its global development. We focused on common challenges, enabling factors, and strategies that have influenced the professionalization of GC across diverse contexts. An exploratory qualitative study was conducted through interviews with key professionals who actively contribute to the field's growth worldwide. Data were analyzed using reflexive thematic analysis, leading to the identification of three overarching themes that reflect upon the establishment and growth of the GC profession: (a) misunderstandings about the profession; (b) diverse routes in its evolution; and (c) strategies for its development and recognition. Findings indicate that the profession tends to evolve through four recurring stages: early, emerging, established, and consolidated, which are repeated across countries, with local variation. This study documents global patterns in the progress of the GC profession and translates them into a practical set of frequently asked questions (FAQs), purposely designed to support decision-makers, educators, and practitioners in advancing understanding, recognition, regulation, and equitable access to GC services worldwide. These FAQs explore whether GC is a distinct profession, its practice model, and the actual roles genetic counselors perform. It examines skills required, title consistency, and how well other healthcare professionals and consultands (affected patients and families) understand the role of GCs. It also highlights the impact of GCs on healthcare efficiency and patient outcomes.
The prognosis of patients with metastatic/relapsed/refractory Ewing sarcoma (ES) is dismal. Natural killer (NK) cells are highly cytotoxic to ES but limited by resistance within the ES tumor microenvironment (TME). Here we sought to overcome ES resistance to NK cells by a combinatorial immunotherapy approach simultaneously enabling NK tumor-specific-targeting via chimeric antigen receptor (CAR) against a novel ES target interleukin-1 receptor accessory protein (IL1RAP), circumventing transforming growth factor beta (TGFβ)-mediated NK immunosuppression by TGFβ1-imprinting, increasing NK cell antibody-dependent cellular cytotoxicity (ADCC) via an anti-GD2 antibody dinutuximab, and improving NK cell persistence and ADCC by an IL-15 agonist, NKTR-255. Peripheral blood mononuclear cells were expanded into NK and TGFβ1-imprinted-NK (imNK) cells using antigen-presenting feeder cells co-expressing IL-21 and 4-1 BBL. Anti-IL1RAP-CAR messenger RNA was electroporated into NK or imNK cells. In vitro cytotoxicity assays were performed to investigate the efficacy of anti-IL1RAP-CAR-NK/imNK cell alone or combined with NKTR-255 and/or dinutuximab against ES cells. Xenograft mouse models of ES were used to investigate the antitumor efficacy of the combinatorial CAR-NK/imNK cell therapy against ES in vivo. Single-cell RNA sequencing and mass cytometry analyses of cells from xenograft tumors were performed to identify mechanisms of response/resistance to this combinatorial immunotherapy. We found that anti-IL1RAP-CAR-NK cells significantly and specifically enhanced NK cytotoxicity in vitro and decreased tumor growth and lung metastasis in vivo against IL1RAP+ES. TGFβ1-imprinting significantly enhanced in vitro cytotoxicity and tumor infiltration of CAR-NK cells, leading to significantly reduced tumor growth and improved animal survival in the ES orthotopic mouse model. Compared with single agent or double combinations, the triple combination of imprinted-CAR-NK (CAR-imNK) cells and NKTR-255 with dinutuximab had superior antitumor efficacy against IL1RAP+GD2+ ES. Mechanistic studies on single cells from the xenograft tumors revealed increased apoptosis of ES cells, upregulated expression of ligands to NK inhibitory receptors on ES cells, and enhanced mouse macrophage migration in the ES TME in response to the CAR-imNK+NKTR-255+dinutuximab therapy. Our preclinical data demonstrate that combinatorial innate immunotherapy leveraging tumor-targeting TGFβ1-imprinted IL1RAP-CAR-NK cells combined with an IL-15 agonist and an anti-GD2 antibody is a promising novel therapeutic strategy for targeting metastatic/relapsed/refractory ES.
Malignant tumor treatment still faces issues like insufficient targeting, drug resistance, and immunosuppression. Spherical nucleic acids (SNAs), with their three-dimensional core-shell structure and densely packed, radially oriented oligonucleotide shell, enable transfection-free cellular uptake and provide nuclease resistance and stability. This review examines SNA engineering strategies and their impact on precision oncology. Functionalization with antibodies, aptamers, or antisense oligonucleotides enables SNAs to target key molecules such as human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and toll-like receptors (TLRs). Advances in stimuli-responsive, self-assembled, liposomal, and peptide-based carrier systems facilitate controlled drug release and modulation of the tumor microenvironment (TME). Diagnostic applications of SNAs include electrochemical, fluorescent, and colorimetric sensing systems for detecting biomarkers such as exosomes, miRNAs, alpha-methylacyl-CoA racemase (AMACR), and telomerase. Therapeutically, SNAs co-deliver chemotherapeutics and immunoadjuvants, support cancer vaccines, and exert efficacy in various tumors, including the central nervous, reproductive, digestive, hematological, barrier, and respiratory systems. Early clinical studies indicate a favorable biosafety profile, but issues remain regarding delivery efficiency, target selectivity, scalability, and long-term safety. Progress toward biodegradable, machine-learning-guided SNA platforms may soon make this nanotechnology a fundamental part of personalized, precision cancer medicine.
Efficient nucleic acid extraction and purification are fundamental to cellular and molecular biology research but remain challenging for large-scale clinical RNA sequencing and PCR assays. This chapter introduces BLADE-R, a novel magnetic bead-based protocol that streamlines the RNA extraction process. BLADE-R integrates cell lysis and nucleic acid binding into a single step, followed by an innovative on-bead rinse to achieve nuclease-free separation of genomic DNA and RNA. The protocol's adaptability to a 96-well plate format enables simultaneous RNA purification from up to 96 human blood samples, significantly reducing time compared with single-sample methods. In this high-throughput setup, BLADE-R demonstrated no cross-contamination between wells during RNA purification, cDNA synthesis, and PCR. BLADE-R's versatility, efficiency, and suitability for low- and high-throughput applications make it an ideal method for RNA preparation in clinical and research settings, particularly for detecting and measuring chimeric RNAs using RT-PCR and sequencing assays. This protocol is especially advantageous in resource-limited environments, facilitating robust and scalable RNA extraction workflows.
Olaparib, a clinically established poly (ADP-ribose) polymerase (PARP) inhibitor widely used in oncology, has significantly improved outcomes in several malignancies. However, increasing evidence indicates that olaparib may induce hepatocellular injury through mechanisms involving oxidative stress, inflammation, and mitochondrial dysfunction. Adenosine triphosphate (ATP), a key regulator of cellular bioenergetics and redox homeostasis, may confer protection against oxidative tissue injury. This study investigated the hepatoprotective effects of ATP against olaparib-induced oxidative liver damage in rats and compared its efficacy with melatonin. Twenty-four male albino Wistar rats were randomly assigned to four experimental groups (n = 6): healthy control (HG), olaparib-treated (OLP), ATP plus olaparib (ATOL), and melatonin plus olaparib (MLOL). Olaparib was administered at a dose of 100 mg/kg orally twice daily, whereas ATP (5 mg/kg, intraperitoneally) and melatonin (10 mg/kg, orally) were administered once daily. The treatments were administered for 14 consecutive days. Hepatic oxidative and inflammatory status was assessed by measuring malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-6 (IL-6) and ATP levels in liver tissue. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured as biochemical indicators of hepatocellular injury. Liver tissues were also examined histopathologically. Olaparib administration significantly increased hepatic MDA and IL-6 levels together with serum ALT and AST activities, while significantly reducing hepatic tGSH and ATP levels and SOD and CAT activities compared with the healthy group (p < 0.001). Both ATP and melatonin significantly attenuated these alterations (p < 0.001). Notably, ATP demonstrated a more pronounced protective effect than melatonin, particularly in suppressing aminotransferase elevations and improving histopathological liver architecture. ATP significantly alleviates olaparib-induced hepatotoxicity by attenuating oxidative stress, suppressing inflammatory responses, restoring antioxidant defense mechanisms and significantly replenishing depleted hepatic ATP levels. These findings suggest that ATP may represent a promising therapeutic strategy for preventing PARP inhibitor-associated drug-induced liver injury.
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by pathogenic variants in the DMD gene, which encodes dystrophin, a cytoskeletal protein linking intracellular actin to the extracellular matrix via the dystrophin-associated protein complex and maintaining muscle fiber integrity. With the emergence of disease-modifying therapies, early and accurate molecular diagnosis is increasingly important. Whole-exome sequencing (WES) is widely used to evaluate unexplained hyperCKemia and distinguish DMD from other inherited neuromuscular disorders. WES identified a novel hemizygous frameshift variant in DMD (NM_004006.3:c.6050_6051del; p.Leu2017Profs*5) in a Taiwanese boy with markedly elevated creatine kinase levels (> 10,000 U/L) and clinical features consistent with DMD. The variant was classified as likely pathogenic according to ACMG criteria (PVS1, PS2, PP3). Comparative genomic analysis demonstrated strong evolutionary conservation at the variant site within the 16th spectrin-like repeat (exon 42), with phastCons scores of 1 and phyloP scores of +2.925 and +1.015. AlphaFold-based structural modeling suggested disruption of the three-helix bundle architecture, while CHARMM-based energy analysis suggested a potential destabilizing effect that appeared more consistent with previously reported pathogenic exon 42 frameshift variants than with benign missense variants at the same locus. This is the first reported case of DMD associated with the novel frameshift variant c.6050_6051del (p.Leu2017Profs*5). Integrated genomic, evolutionary, and structural analyses support the likely pathogenic interpretation of this variant. This study expands the mutational spectrum of DMD and highlights the value of combining WES with structure-informed approaches for variant interpretation. These findings provide preliminary structural insights into the potential effects of the identified variant and highlight the possible utility of structure-informed variant interpretation in the absence of functional assays.
The shapes and material properties of cotton (Gossypium spp.) seed coat trichoblasts form the basis of a multibillion-dollar natural fiber industry. As such, these highly specialized cells are low-hanging fruit for intentional trait engineering. However, broad success will require more mechanistic knowledge of their systems-level cellular controls. This time-series study integrates daily measurements of purified fiber transcriptomes and proteomes with multiscale fiber phenotyping datasets that span the same developmental interval. Abundance profiles of the subcellular proteomes are the foundation of the analyses. This resource article provides direct information about which homoeologs operate and offers informative depictions of how compartmentalized cellular systems change during developmental transitions. Prediction accuracy was partially validated by analyzing protein expression group 11, which contained multiple known secondary cell wall (CW) cellulose synthases together with dozens of unknown proteins, and displayed an averaged expression profile that strongly correlated with a sharp state transition in cellulose microfibril alignment and increased cellulose content. The dataset as a whole can serve as a hypothesis-generating tool to guide future experiments related to CW glycome remodeling, morphogenesis, reversible tissue formation, and growth rate control. Integration of mRNA and protein abundance revealed widespread evidence of post-transcriptional control. In addition, there were hundreds of transcriptionally controlled genes with different time points of transition. This latter gene set can be used to more reliably analyze transcriptional control networks and to generate collections of gene expression drivers for cotton fiber research. The protein and transcript abundance profiles are organized into user-friendly tables and a web interface that can be searched using any plant ortholog of interest based on developmental time, abundance, annotations, or phenotypic association.
Retinopathy of prematurity (ROP)-associated vision loss is driven by pathological retinal angiogenesis. Current therapies suppress neovascularization but do not fully restore vascular integrity or prevent long-term visual deficit. Activation of the sigma-1 receptor (Sig1R) has been reported to confer neuroprotection, yet its role in retinal vascular protection remains largely unexplored. Here, we investigated whether Sig1R activation confers vascular protection in experimental ROP. The oxygen-induced retinopathy (OIR) mouse model was induced in wild-type and Sig1R-/- mice with or without systemic (+)-pentazocine ([+]-PTZ) administration to activate Sig1R. Retinal vascular pathology, barrier integrity, and avascular areas were evaluated by fluorescein angiography and retinal flatmount analysis. Molecular changes in metabolic, oxidative, and inflammatory pathways were assessed by immunostaining/blotting and ELISA assay. Sig1R expression was reduced in OIR retinas, accompanied by decreased cullin-3 ubiquitin ligase (Cul3) and phosphorylated AMP-activated protein kinase (pAMPK) and increased pAkt and endothelial nitric oxide synthase (eNOS), indicative of metabolic and endothelial stress. Activation of Sig1R with (+)-PTZ restored Sig1R, Cul3, and pAMPK levels, suppressed pAkt/eNOS signaling, reduced oxidative stress, and attenuated Müller glial activation. OIR-induced upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and pro-angiogenic/inflammatory mediators, including vascular endothelial growth factor (VEGF), IL-6, TNF-α, macrophage colony-stimulating factor (M-CSF), vascular cell adhesion molecule 1 (VCAM-1), and tumor necrosis factor receptor (TNFR), were markedly reduced by (+)-PTZ. Functionally, Sig1R activation improved retinal vascular barrier integrity, reduced arterial tortuosity and pathological neovascularization, and promoted revascularization of avascular retina. Importantly, (+)-PTZ treatment failed to confer any vascular benefit in Sig1R-/- mice, confirming that these vascular benefits are Sig1R dependent. Sig1R activation preserves vascular integrity and suppresses pathological angiogenesis in OIR. Together with known neuroprotective effects, Sig1R represents a promising dual neurovascular therapeutic target for ROP.
Anthropogenic stressors leading to environmental pollution and subsequent climate change are emerging as a global concern. Consequently, the quality of the major environmental components, such as air, water, and soil is deteriorating, adversely affecting the overall ecosystem functioning. In this regard, bioindicators play a vital role in assessing environmental alterations and their implications for the functional integrity of ecosystems. Microbial bioindicators exhibit noticeable changes in physiological, behavioural and diversity patterns, in response to the changing environmental conditions. Among them, the microscopic indicators, including bacteria, fungi, protists, plankton and lichen show remarkable sensitivity towards environmental alterations due to their comparatively simple cellular processes. They respond to environmental disturbances in terms of distinctive characteristics, including bioluminescence, pathogenicity, pigmentation, altered diversity, photosynthetic responses and chemical degradation. Essentially, they serve as critical bioindicators of potentially polluted or unpolluted environments. Moreover, these microbial biomarkers not only signal environmental degradation but also provide early warning signals, further maintaining the ecosystem stability. Despite their reported application in environmental assessment, knowledge of microbial indicator mechanisms, ecological interactions, and emerging bioengineering approaches remains fragmented. Overall, microbial bioindicators serve as valuable monitoring tools, due to their ecological significance, indicator mechanisms, applications in biomonitoring, and recent advances in engineered biosensing approaches. Advances in molecular biology, microbial diversity assessment, and microbial bioengineering approaches exhibit significant potential for enhancing environmental biomonitoring.
AbstractEdwardsia elegans Verrill, 1869 is the most commonly encountered and discussed species of Edwardsia from North America. Although it is familiar and commonly cited in field guides, its anatomy, cnidom, life history, and molecular resources have been only partially described. We provide a full account of E. elegans, along with an annotated transcriptome, and differentiate it from other species of Edwardsia from the western North Atlantic. We also describe the juvenile morphology and natural history of E. elegans, based on in situ observations in Maine and ex situ observations of captive specimens maintained in an aquarium. Edwardsia elegans is distinguished from all other edwardsiids from North America in having 16 tentacles arrayed in two cycles of eight, nemathybomes forming distinct aggregations in the middle of each mesenterial compartment, and a bulbous physa. Adults burrow using their physa and tend to aggregate into clusters in the field and the lab. Analysis of the transcriptome reveals differences in content of genes related to cellular stress with a broadly studied edwardsiid species, Nematostella vectensis. This updated account and the availability of reference sequence data for E. elegans will be useful for future research with this species and comparative work across edwardsiid anemones and the Cnidaria.
Ferns are well known for their exceptionally large genomes and high chromosome numbers, which may be in part due to whole genome duplications (WGDs) followed by slow diploidization. To better understand the mode of fern genome evolution, we focus on the heterosporous fern genus Salvinia, which exhibits striking variation in genome size and chromosome number. We generated chromosome-level genome assemblies for Salvinia cucullata, the fern with the smallest genome, and Salvinia molesta, a globally invasive species widely thought to be an allopentaploid. Surprisingly, we found that S. molesta is in fact a diploid hybrid and that S. cucullata, despite having a genome ten times smaller than S. molesta, has substantially more chromosomes. Both species lack any recent WGDs and their highly variable genomes were predominately shaped by transposable element proliferation and chromosome rearrangements. The complete decoupling of chromosome number and genome size in Salvinia sharply contrasts the typical pattern in ferns, which are mostly homosporous and produce only one type of spore by meiosis. Many of the genome features observed in Salvinia are consistent with genomic changes due to female meiotic drive, a mechanism possible only in heterosporous plants that produce distinct microspores and megaspores. These results redefine the genetic identity of S. molesta and provide insights into its invasive success. The marked variation in genome composition and structure within Salvinia challenges the prevailing model of fern genome evolution while aligning with expectations for angiosperms, another heterosporous lineage.
Medication errors, often arising from insufficient pharmacology knowledge, can have serious consequences, highlighting the importance of effective pharmacology education for health care students. This study hypothesized that virtual reality (VR) could improve student engagement, motivation and perceived learning of core concepts in pharmacology. A mixed-method approach was employed. Students who had completed a course in basic pharmacology were recruited from five international study sites to view a VR animation, explaining drug absorption and bioavailability. The students responded to an online questionnaire exploring their experience and understanding. In addition, 13 medical students from the University of Bergen participated in focus group interviews to further explore their perceptions of VR in pharmacology education. A total of 133 students participated in the VR session and completed the questionnaire, with approximately half reporting that the VR animation changed their understanding of drug absorption. Thematic analysis of the focus group interviews produced three themes descriptive of the students' learning experiences, each pivoting tensions between: (1) The role of VR in integrating pharmacology with other medical disciplines; (2) striking a balance between engaging and overwhelming learning experiences; (3) in-depth learning under the weight of assessment. The technical solution appears satisfactory, and students found the 360° VR animation engaging and useful for visualizing the complex concepts of absorption and bioavailability. VR animation shows potential to enhance integration of pharmacology to other medical disciplines. However, careful design is required to support self-paced learning and minimize cognitive overload.
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide, with India alone contributing nearly 27% of the global PTB burden. Although alterations in the vaginal microbiome have been implicated in PTB, its association in the Indian context is underexplored. This study aimed to investigate the association of the vaginal microbiome and PTB in Indian women at the time of delivery. The vaginal swabs were collected at the time of delivery from 72 women (31 term, 41 preterm) admitted to a tertiary care hospital in Western India. Microbial DNA was extracted, and the V3-V4 region of the 16S rRNA gene was sequenced. Community composition, alpha and beta diversity, and differential taxonomic abundance were assessed using bioinformatics pipelines. There were no significant differences in alpha or beta diversity between term and preterm groups. Principal coordinate and unsupervised clustering analyses showed no group-wise segregation. The relative abundance of individual Lactobacillus species, including L. iners and L. helveticus, did not differ significantly between the two groups. However, a modest difference in the relative abundance of Streptococcus was observed between the two groups after adjustment. This study found no major microbial shifts in the vaginal microbiome associated with preterm birth in this cross-sectional cohort of Indian women, suggesting that vaginal dysbiosis at the time of delivery may not be a principal driver of PTB in this population. These findings underscore the need for larger, longitudinal, and ethnically diverse studies using standardized methodologies better to understand the microbiome's role in PTB risk.
Icosahedral viruses organize and compact their genomes within volumetrically constrained capsids. Double-stranded (ds) DNA viral genomes form ordered spool-like structures when packaged into preformed capsids. By contrast, single-stranded (ss) RNA viral coat proteins recognize genomic sequences or structures, nucleating assembly around folded genomes. A similar mechanism may occur in some ssDNA systems; however, in parvo- and microviruses, the ss genome is concurrently synthesized and packaged into a preformed shell. In the øX174 X-ray virion structure, only ~12% of the genome is ordered. Consequently, the mechanism by which the genome is accommodated within the constrained capsid remains obscure. Sequence motifs within the øX174 genome produce a periodic segmentation pattern consistent with T = 1 icosahedral symmetry. To determine the function of these motifs, a subset within the first five packaged segments was altered. No regulatory elements or encoded amino acids were changed. The resulting mutant, øXDO5, displayed a phenotype consistent with those of previously characterized packaging mutants. To further understand this phenomenon, the DNA replication-packaging pathway was characterized in cells co-infected with wild-type and øXDO5. Each genome could both be separately tracked and distinguished throughout the pathway. Early, pre-packaging øXDO5 genome replication was comparable to the wild-type. However, øXDO5 genomes were severely diminished within virions, suggesting a defect in the transition from packaging intermediates to mature virions.IMPORTANCEConcurrent genome biosynthesis and packaging are specific to some families of single-stranded (ss) DNA icosahedral viruses. This evolutionary strategy combines elements found in both dsDNA and ssRNA systems. Like dsDNA viruses, the genome is packaged into a preformed capsid. Like ssRNA viruses, there are numerous capsid-genome associations. However, in microviruses, such as øX174, these interactions do not facilitate capsid assembly around the genome. They occur after the ss genome enters the preformed procapsid. Sequence motifs within the øX174 genome produce a periodic segmentation pattern consistent with T = 1 icosahedral symmetry. The data provided herein demonstrate that altering these periodic motifs can lead to packaging defects, suggesting an additional level of selective pressure acting on ssDNA genomes.