aBIOTECH. 2025 Jan 23;6(1):116-132. doi: 10.1007/s42994-024-00194-0. eCollection 2025 Mar.

ABSTRACT

Plant metabolites are crucial for the growth, development, environmental adaptation, and nutritional quality of plants. Plant metabolomics, a key branch of systems biology, involves the comprehensive analysis and interpretation of the composition, variation, and functions of these metabolites. Advances in technology have transformed plant metabolomics into a sophisticated process involving sample collection, metabolite extraction, high-throughput analysis, data processing, and multidimensional statistical analysis. In today's era of big data, the field is witnessing an explosion in data acquisition, offering insight into the complexity and dynamics of plant metabolism. Moreover, multiple omics strategies can be integrated to reveal interactions and regulatory networks across different molecular levels, deepening our understanding of plant biological processes. In this review, we highlight recent advances and challenges in plant metabolomics, emphasizing the roles for this technique in improving crop varieties, enhancing nutritional value, and increasing stress resistance. We also explore the scientific foundations of plant metabolomics and its applications in medicine, and ecological conservation.

PMID:40060186 | PMC:PMC11889285 | DOI:10.1007/s42994-024-00194-0

Front Microbiol. 2025 Feb 21;15:1462941. doi: 10.3389/fmicb.2024.1462941. eCollection 2024.

ABSTRACT

Permafrost thaw increases the bioavailability of ancient organic matter, facilitating microbial metabolism of volatile organic compounds (VOCs), carbon dioxide, and methane (CH4). The formation of thermokarst (thaw) lakes in icy, organic-rich Yedoma permafrost leads to high CH4 emissions, and subsurface microbes that have the potential to be biogeochemical drivers of organic carbon turnover in these systems. However, to better characterize and quantify rates of permafrost changes, methods that further clarify the relationship between subsurface biogeochemical processes and microbial dynamics are needed. In this study, we investigated four sites (two well-drained thermokarst mounds, a drained thermokarst lake, and the terrestrial margin of a recently formed thermokarst lake) to determine whether biogenic VOCs (1) can be effectively collected during winter, and (2) whether winter sampling provides more biologically significant VOCs correlated with subsurface microbial metabolic potential. During the cold season (March 2023), we drilled boreholes at the four sites and collected cores to simultaneously characterize microbial populations and captured VOCs. VOC analysis of these sites revealed "fingerprints" that were distinct and unique to each site. Total VOCs from the boreholes included > 400 unique VOC features, including > 40 potentially biogenic VOCs related to microbial metabolism. Subsurface microbial community composition was distinct across sites; for example, methanogenic archaea were far more abundant at the thermokarst site characterized by high annual CH4 emissions. The results obtained from this method strongly suggest that ∼10% of VOCs are potentially biogenic, and that biogenic VOCs can be mapped to subsurface microbial metabolisms. By better revealing the relationship between subsurface biogeochemical processes and microbial dynamics, this work advances our ability to monitor and predict subsurface carbon turnover in Arctic soils.

PMID:40059907 | PMC:PMC11885255 | DOI:10.3389/fmicb.2024.1462941

J Exp Bot. 2025 Mar 10:eraf100. doi: 10.1093/jxb/eraf100. Online ahead of print.

ABSTRACT

Hydrogen sulfide (H2S) is increasingly recognized as a crucial signaling molecule in plants, playing key roles in regulating physiological processes and enhancing stress tolerance. This review provides an updated summary of H2S signaling in plant stress responses, discussing its uptake from external environmental sources, its endogenous biosynthesis, and its broader functions in stress adaptation. We summarize the impact of H2S on plants under various stress conditions and review the mechanisms through which it mediates signaling functions, with a particular focus on H2S-mediated protein persulfidation. Additionally, we provide an overview of the current understanding of protein persulfidation in regulating physiological processes and stress responses in plants, offering both a general discussion of its effects under different stress conditions and specific examples to highlight its significance. Finally, we review recent proteomic studies on protein persulfidation in plants, comparing the identified persulfidated proteins across studies and highlighting shared biological processes and pathways. This review aims to consolidate the current understanding of H2S signaling and its roles mediated by protein persulfidation in plants, while also offering insights to inspire future research in this rapidly evolving field.

PMID:40059712 | DOI:10.1093/jxb/eraf100

Genetics. 2025 Mar 10:iyaf025. doi: 10.1093/genetics/iyaf025. Online ahead of print.

ABSTRACT

Tissue-regulated alternative exons are dictated by the interplay between cis-elements and trans-regulatory factors such as RNA binding proteins. Despite extensive research on splicing regulation, the full repertoire of these cis and trans features and their evolutionary dynamics across species are yet to be fully characterized. Members of the CUG-binding protein and ETR-like family (CELF) of RNA binding proteins are known to play a key role in the regulation of tissue-biased splicing patterns, and when mutated, these proteins have been implicated in a number of neurological and muscular disorders. In this study, we sought to characterize specific mechanisms that drive tissue-specific splicing in vivo of a model switch-like exon regulated by the neuronal-enriched CELF ortholog in C. elegans, UNC-75. Using sequence alignments, we identified deeply conserved intronic UNC-75 binding motifs overlapping the 5' splice site and upstream of the 3' splice site, flanking a strongly neural-repressed alternative exon in the Zonula Occludens gene zoo-1. We confirmed that loss of UNC-75 or mutations in either of these cis-elements lead to substantial de-repression of the alternative exon in neurons. Moreover, mis-expression of UNC-75 in muscle cells is sufficient to induce the neuron-like robust skipping of this alternative exon. Lastly, we demonstrate that overlapping an UNC-75 motif within a heterologous 5' splice site leads to increased skipping of the adjacent alternative exon in an unrelated splicing event. Together, we have demonstrated that a specific configuration and combination of cis elements bound by this important family of RNA binding proteins can achieve robust splicing outcomes in vivo.

PMID:40059624 | DOI:10.1093/genetics/iyaf025

Small Methods. 2025 Mar 9:e2500136. doi: 10.1002/smtd.202500136. Online ahead of print.

ABSTRACT

Mechanical strain substantially influences tissue shape and function in various contexts from embryonic development to disease progression. Disruptions in these processes can result in congenital abnormalities and short-circuit mechanotransduction pathways. Manipulating strain in live tissues is crucial for understanding its impact on cellular and subcellular activities, unraveling the interplay between mechanics and cells. Existing tools, such as optogenetic modulation of strain, are limited to small strains over limited distances and durations. Here, a high-strain stretcher system, the TissueTractor, is introduced to enable simultaneous high-resolution spatiotemporal imaging of live cells and tissues under strain applications varying from 0% to over 100%. We use the system with organotypic explants from Xenopus laevis embryos, where applied tension reveals cellular strain heterogeneity and remodeling of intracellular keratin filaments. To highlight the device's adaptability, the TissueTractor is also used to study two other mechanically sensitive cell types with distinct physiological roles: human umbilical vein endothelial cells and mouse neonatal cardiomyocytes, revealing cell morphological changes under significant strain. The results underscore the potential of the TissueTractor for investigating mechanical cues that regulate tissue dynamics and morphogenesis.

PMID:40059484 | DOI:10.1002/smtd.202500136

Brain Behav Immun. 2025 Mar 7:S0889-1591(25)00099-6. doi: 10.1016/j.bbi.2025.03.013. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals raised in an urban environment (URBANs) show an exaggerated inflammatory response to the Trier Social Stress Test (TSST) compared with individuals raised in a rural environment. The underlying mechanisms are unclear but may relate to childhood animal contact. As an exaggerated immune (re)activity plays a causal role in the pathogenesis of stress-associated disorders, these findings might explain the higher prevalence of stress-associated disorders in urban vs. rural areas.

METHODS: We recruited physically and emotionally healthy male URBANs, raised in a city with more than 40,000 residents either in the absence (noPETs) or presence (PETs) of household pets. Participants were individually exposed to the TSST, and before and after the TSST, blood and saliva were collected for assessment of different stress-related parameters. An additional saliva sample before the TSST was collected for salivary microbiome analysis. Heart rate (HR) and HR variability (HRV) were recorded continuously. Mental and physical health status, early-life and perceived life stress, current animal contact, and subjective strain induced by TSST exposure were assessed using validated questionnaires.

RESULTS: Here we show that adult healthy male URBANs raised in the absence (noPETs) vs. presence (PETs) of household pets still reported less animal contact during adulthood and were characterized by deficits in their immunoregulatory and intestinal barrier function, which under basal conditions did not translate into a chronic low-grade inflammatory state. This was different under acute psychosocial stress conditions. Exposure to the TSST resulted in a facilitated mobilization of particularly neutrophil granulocytes in noPETs vs. PETs, accompanied by an enhanced pro- and compromised anti-inflammatory systemic stress response.

CONCLUSION: Together, the presence of pets seems to reduce the risk for URBANs to develop stress-associated disorders later in life (i.e., primary prevention) by facilitating immunoregulatory and barrier functions, in turn preventing an overshooting immune activation in response to acute stressors and chronic low-grade inflammation in response to repeated/chronic stressors.

PMID:40058670 | DOI:10.1016/j.bbi.2025.03.013

BMB Rep. 2025 Mar 5:6350. Online ahead of print.

ABSTRACT

Abscisic acid (ABA) is a key phytohormone that regulates multiple biological processes in plants, including seed germination, seedling growth, and abiotic stress response. ABA enhances drought tolerance by promoting stomatal closure, thereby improving crop productivity under unfavorable stress conditions. Extensive research efforts have focused on understanding ABA signaling more clearly for its potential application in agriculture. The accumulation and stability of signaling components involved in the efficient transduction of downstream ABA signaling are affected by both transcriptional regulation and post-translational modifications. Ubiquitination is a representative post-translational modification that regulates protein stability, and E3 ubiquitin ligase is a key enzyme that determines target substrates for ubiquitination. To date, many E3 ligases functioning as a monomeric form such as RING-, HECT- and Ubox-types have been known to participate in the ABA signaling process. In this review, we summarize the current understanding of ABA-related monomeric E3 ligases, their regulation, and mode of action in Arabidopsis, which will help develop a detailed and integrated understanding of the ABA signaling process in Arabidopsis.

PMID:40058874

J Biotechnol. 2025 Mar 7:S0168-1656(25)00063-X. doi: 10.1016/j.jbiotec.2025.03.006. Online ahead of print.

ABSTRACT

Transaminases have important applications in the synthesis of drug intermediates such as chiral amines. However, natural transaminases exhibit suboptimal thermal stability, limiting their further applications. Building upon an Rhodobacter sp.-derived (R)-selective transaminase (RbTA), we report a dual-region coupling engineering approach to improve thermostability of RbTA by strengthening the core hydrogen-bond networks and rigidifying the flexible surface loop. Through single strategy, we identified 4 thermostability improved single mutations, among which I249Q demonstrated the most substantial improvement, achieving a 18-fold increase in half-life (t1/240) and a 11.2 ℃ increase in T5010. Then in strategic coupling, the synergistic effect of dual-region modification was observed in both thermal stability and activity enhancement, as mutant with the best high-temperature catalytic performance, R136P/F228Y, had its T5010 improved by 7.1℃ and exhibited a 4.2-fold increase in kcat/Km towards (R)-3-amino-1-butanol. Finally, R136P/F228Y achieved a 20.5% improvement in conversion over WT in an analytical-scale synthesis in 72h at a 5 ℃ elevated catalytic temperature. Molecular dynamics simulations demonstrated that the synergy of the formation of new hydrogen bonds and decrease in flexibility accounted for the thermostability improvements. This study provides guidance for enhancing thermostability of similar fold-type enzymes without impairing enzymatic activity in an efficient manner.

PMID:40058651 | DOI:10.1016/j.jbiotec.2025.03.006

Mol Cell Proteomics. 2025 Mar 7:100934. doi: 10.1016/j.mcpro.2025.100934. Online ahead of print.

ABSTRACT

Limited proteolysis combined with mass spectrometry (LiP-MS) facilitates probing structural changes on a proteome-wide scale. This method leverages differences in the proteinase K accessibility of native protein structures to concurrently assess structural alterations for thousands of proteins in situ. Distinguishing different contributions to the LiP-MS signal, such as changes in protein abundance or chemical modifications, from structural protein alterations remains challenging. Here, we present the first comprehensive computational pipeline to infer structural alterations for LiP-MS data using a two-step approach. (1) We remove unwanted variations from the LiP signal that are not caused by protein structural effects and (2) infer the effects of variables of interest on the remaining signal. Using LiP-MS data from three species we demonstrate that this approach outperforms previously employed approaches. Our framework provides a uniquely powerful approach for deconvolving LiP-MS signals and separating protein structural changes from changes in protein abundance, post-translational modifications and alternative splicing. Our approach may also be applied to analyze other types of peptide-centric structural proteomics data, such as FPOP or molecular painting data.

PMID:40058498 | DOI:10.1016/j.mcpro.2025.100934

Cell Rep. 2025 Mar 7;44(3):115392. doi: 10.1016/j.celrep.2025.115392. Online ahead of print.

ABSTRACT

Streptomyces albidoflavus is a widely used strain for natural product discovery and production through heterologous biosynthetic gene clusters (BGCs). However, the transcriptional regulatory network (TRN) and its impact on secondary metabolism remain poorly understood. Here, we characterize the TRN using independent component analysis on 218 RNA sequencing (RNA-seq) transcriptomes across 88 unique growth conditions. We identify 78 independently modulated sets of genes (iModulons) that quantitatively describe the TRN across diverse conditions. Our analyses reveal (1) TRN adaptation to different growth conditions, (2) conserved and unique characteristics of the TRN across diverse lineages, (3) transcriptional activation of several endogenous BGCs, including surugamide, minimycin, and paulomycin, and (4) inferred functions of 40% of uncharacterized genes in the S. albidoflavus genome. These findings provide a comprehensive and quantitative understanding of the S. albidoflavus TRN, offering a knowledge base for further exploration and experimental validation.

PMID:40057950 | DOI:10.1016/j.celrep.2025.115392

Best Pract Res Clin Endocrinol Metab. 2025 Mar 3:101985. doi: 10.1016/j.beem.2025.101985. Online ahead of print.

ABSTRACT

Primary hyperparathyroidism is a common endocrine disorder characterized by inappropriate elevation of parathyroid hormone and hypercalcemia. While predominantly an asymptomatic disease in Western populations, symptomatic presentations are more prevalent in Eastern countries. The molecular pathogenesis of sporadic PHPT primarily involves genetic and epigenetic alterations leading to abnormal parathyroid cell proliferation and altered calcium sensing mechanism. To date, MEN1 and cyclin D1 are the only established drivers of sporadic PHPT. Somatic MEN1 gene mutations occur in 30-40 % of sporadic parathyroid adenomas (PA), with a recent study on symptomatic cases reporting germline variants.Cyclin D1 overexpression in sporadic PA has been observed in 20-40 % of cases in Western populations and 80 % of cases in Eastern populations, with an inverse association with cyclin-dependent kinase inhibitors CDKN2A and CDKN2B expression. The calcium-sensing receptor expression was significantly lower in symptomatic compared to asymptomatic PHPT, strongly supported by epigenetic deregulation (promoter hypermethylation and histone methylation). Recent studies have highlighted the potential involvement of EZH2, a histone methyltransferase, in parathyroid tumorigenesis. Additionally, parathyroid-specific transcription factors like GCM2, PAX1, and GATA3 are emerging as putative tumor suppressors, especially from the symptomatic PHPT. Next-generation sequencing has identified novel potential drivers such as PIK3CA, MTOR, and NF1 in sporadic PC, alongside CDC73. The molecular landscape of sporadic PHPT appears to differ between Eastern and Western populations. This heterogeneity underscores the need for further large-scale studies, particularly in symptomatic cases from developing nations, to comprehensively elucidate the molecular drivers of parathyroid tumorigenesis.

PMID:40057423 | DOI:10.1016/j.beem.2025.101985

Biochim Biophys Acta Mol Basis Dis. 2025 Mar 6:167781. doi: 10.1016/j.bbadis.2025.167781. Online ahead of print.

ABSTRACT

Non-coding RNAs (ncRNAs) are frequently dysregulated in various cancers and have been implicated in the etiology and progression of cancer. Ovarian cancer, the most fatal gynecological cancer, has a poor prognosis and a high patient fatality rate due to metastases. In this study, we classified patients with ovarian cancer into three groups based on their ncRNA expression levels. Notably, an ncRNA transcribed by RNA polymerase III, RNA component of mitochondrial RNA processing endoribonuclease (RMRP), is highly expressed in a group with a poor prognosis. Functional assays using SKOV3 and HeyA8 human ovarian cancer cell lines revealed that while RMRP modulation had no significant effect on cell viability, it markedly enhanced cell invasion. Knockdown and ectopic expression experiments demonstrated that RMRP promotes the secretion of matrix metalloproteinase (MMP)-2 and -9, thereby facilitating ovarian cancer cell invasiveness. Transcriptomic analysis further revealed a positive correlation between RMRP expression and genes involved in cellular localization, including RAB31, a member of the Ras-related protein family. Notably, RAB31 knockdown abrogated the pro-invasive effects of RMRP, identifying it as a key downstream effector in SKOV3 and HeyA8 cells. In addition, MechRNA analysis identified RAB31 as a putative RMRP-interacting transcript. These findings establish RMRP as a critical regulator of RAB31-dependent MMP secretion and ovarian cancer cell invasion. Moreover, our results suggest that RMRP could serve as a promising prognostic biomarker for ovarian cancer.

PMID:40057205 | DOI:10.1016/j.bbadis.2025.167781

Environ Toxicol Pharmacol. 2025 Mar 6:104672. doi: 10.1016/j.etap.2025.104672. Online ahead of print.

ABSTRACT

5-hydroxy-N,N-dimethyltryptamine (5-OH-DMT), known as bufotenine, is proven to have psychoactive effects in high concentrations. Duttyphrynus melanostictus, which produces bufotenine, has migrated to the city of Toamasina in Madagascar, thus, the determination bufotenine's levels in the species' samples is necessary. This study aimed to quantify bufotenine in eggs, tadpoles and toad's skin samples of the Duttyphrynus melanostictus as well as in its predator Hoplobatrachus tigerinus and Haemopis sanguisiga. Two extraction protocols were applied depending on the sample type both based on liquid liquid extraction. Spiked calibration samples were prepared at six concentration levels (10-1000ng/mL), and performance parameters were evaluated: linearity, accuracy (bias%), precision (CV%) and limit of detection. The proposed protocol is simple and quick, and the UHPLC-MS/MS system used exhibited adequate sensitivity. The target analyte was detected in all samples except for the eggs of Duttyphrynus melanostictus, with concentrations increasing in line with the animal's development.

PMID:40057147 | DOI:10.1016/j.etap.2025.104672

Biomed Pharmacother. 2025 Mar 7;185:117944. doi: 10.1016/j.biopha.2025.117944. Online ahead of print.

ABSTRACT

PURPOSE: To analyze the response of different retinal ganglion cell (RGC) populations to NMDA-induced retinal excitotoxicity and the effect of an intraperitoneal treatment with 7,8-Dihydroxyflavone (DHF), a potent selective TrkB agonist.

METHODS: Adult albino rats were treated the day prior to NMDA injection and the three following days with intraperitoneal vehicle (1 %DMSO in 0.09 %NaCl) or DHF (5 mg/kg in vehicle) injections. DHF-afforded protection was studied in the population of Brn3a+RGCs, OPN+RGCs (α-RGCs), OPN+ Tbr2+RGCs (αONs-RGCs), OPN+ Tbr2-Brn3a-RGCs (αONt-RGCs) and OPN+Brn3a+RGCs (αOFF-RGCs) at 3,7,14, or 21 days. The functional response was analyzed longitudinally with full-field electroretinograms. The mechanisms underlying DHF-afforded neuroprotection were assessed by western blot (WB) analysis of the levels of phosphorylated and total TrkB, phosphatidylinositol 3 kinase (PIK3/AKT) and mitogen-activated protein kinase (MAPK).

RESULTS: NMDA intravitreal injection resulted in a significant diminution of the mean amplitudes of the pSTR and b-waves, as well as in severe depletion of all RGCs studied except αONt-RGCs. DHF treatment resulted in rescued mean amplitudes of the pSTR and b-waves up to 21 days after NMDA. WB analysis revealed an increase in p-TrkB which correlates to the increase of TRKB protein and an increase in normalized pAKT/AKT. pMAPK/MAPK was upregulated earlier and significantly higher in DHF-treated retinas. DHF afforded survival of up to 49 % of the Brn3a+RGCs versus 25 % of the vehicle group at 21 days after NMDA, and improved survival of the α-RGC and αONs-RGCs but did not rescue the αOFF-RGCs.

CONCLUSION: Different RGC types exhibit variable susceptibilities to NMDA injury, and DHF-mediated activation of TrkB affords neuroprotection.

PMID:40056826 | DOI:10.1016/j.biopha.2025.117944

Talanta. 2025 Mar 4;291:127891. doi: 10.1016/j.talanta.2025.127891. Online ahead of print.

ABSTRACT

Diabetic liver injury (DLI) is a significant complication of diabetes mellitus, leading to severe liver dysfunction and non-alcoholic fatty liver disease (NAFLD). Understanding the metabolic alterations and reprogramming in DLI is critical for identifying therapeutic targets. Despite the prevalence of DLI, its underlying metabolic mechanisms remain poorly understood, and effective treatments are lacking. In this study, we employed a multimodal mass spectrometry imaging approach, combining air-flow-assisted desorption electrospray ionization (AFADESI-MSI) with matrix-assisted laser desorption ionization (MALDI-MSI) to achieve a comprehensive spatial analysis of metabolic changes in DLI model rats, focusing on the potential therapeutic effects of ferulic acid, a compound known for its antioxidant and anti-inflammatory properties. This approach allowed for the wide-coverage and high-resolution visualization of over 200 metabolites in the liver tissues of DLI model rats. The study involved comparing metabolic profiles between control, DLI, and ferulic acid-treated groups, with ferulic acid administered at a dosage of 50 mg/kg daily for 20 weeks. The analysis revealed significant metabolic reprogramming in DLI, characterized by alterations in glucose, lipid, bile acid, and nucleotide metabolism. Specifically, we identified over 100 metabolites with heterogeneous distributions across liver sections, highlighting region-specific metabolic impairments. Ferulic acid treatment notably reversed many of these metabolic disturbances, particularly in glucose and lipid metabolism, suggesting its potential to restore metabolic homeostasis in DLI. This study provides critical insights into the metabolic underpinnings of DLI and demonstrates the therapeutic potential of ferulic acid in modulating these pathways. The findings underscore the utility of AFADESI- and MALDI-MSI in studying liver diseases and suggest that the metabolites identified could serve as novel biomarkers for DLI diagnosis and treatment.

PMID:40056655 | DOI:10.1016/j.talanta.2025.127891

J Neuroinflammation. 2025 Mar 8;22(1):71. doi: 10.1186/s12974-025-03388-5.

ABSTRACT

BACKGROUND: Olfactory dysfunction is an underestimated symptom in multiple sclerosis (MS). Here, we examined the pathogenic mechanisms underlying inflammation-induced dysfunction of the olfactory bulb using the animal model of MS, experimental autoimmune encephalomyelitis (EAE).

RESULTS: Reduced olfactory function in EAE was associated with the degeneration of short-axon neurons, immature neurons, and both mitral and tufted cells, along with their synaptic interactions and axonal repertoire. To dissect the mechanisms underlying the susceptibility of mitral cells, the main projection neurons of the olfactory bulb, we profiled their responses to neuroinflammation by single-nucleus RNA sequencing followed by functional validation. Neuroinflammation resulted in the induction of potassium channel transcripts in mitral cells, which was reflected in increased halothane-induced outward currents of these cells, likely contributing to the impaired olfaction in EAE animals.

CONCLUSION: This study reveals the crucial role of mitral cells and their potassium channel activity in the olfactory bulb during EAE, thereby enhancing our understanding of neuroinflammation-induced neurodegeneration in MS.

PMID:40057769 | DOI:10.1186/s12974-025-03388-5

Evodevo. 2025 Mar 8;16(1):2. doi: 10.1186/s13227-025-00238-6.

ABSTRACT

BACKGROUND: Relatively little is known about the diversity of embryonic development across lineages of spiders, even though the study of embryonic development is a primary step in evo-devo studies and essential for understanding phenotypic evolution. Practically nothing is known about embryogenesis in cave-dwelling spiders, animals which play an important role in cave ecosystems and may have remarkable adaptations to aphotic habitats such as loss of eyes.

RESULTS: Here, we describe embryogenesis and study the expression patterns of several genes of the Retinal Determination Network (RDN) in the troglophile (species that have pre-adaptations to life in caves, and can complete their life cycle in caves, as well as in epigean habitats) eye-bearing funnel-web spider species Tegenaria pagana C. L. Koch, 1840, using fluorescent staining and confocal microscopy. We discuss the characteristic features of T. pagana embryogenesis and key RDN genes. Although in many respects the embryonic development of different species of entelegyne spiders is similar, we found differences in the rate of development, and the details of the opisthosoma, respiratory system, and brain morphogenesis in comparison with established spider model species. Our data supports the hypothesis of a conserved role of sine oculis gene in the eye formation of arachnids.

CONCLUSIONS: Given the recent discovery of congeneric cave species with different degrees of eye reduction throughout Israel, these data sets provide a foundational point of comparison for studying eye reduction and eye loss events in the spider genus Tegenaria.

PMID:40057742 | DOI:10.1186/s13227-025-00238-6

Sci Rep. 2025 Mar 8;15(1):8103. doi: 10.1038/s41598-025-92756-5.

ABSTRACT

Tinospora cordifolia has been used for thousands of years to treat various health conditions, including neurodegenerative diseases. The study aimed to elucidate the mechanism of action and protein targets of T. cordifolia in the context of Alzheimer's disease through untargeted metabolomics and network pharmacology. LC-MS/MS analysis resulted in 1186 metabolites, including known bioactive compounds such as liquiritin, Plastoquinone 3, and Shoyuflavone A, to name a few. The network pharmacology analysis highlighted the metabolite-protein interaction with the enrichment of 591 human proteins, including neurotransmitter receptors and other regulatory proteins. Pathway analysis highlighted the enrichment of cAMP, mTOR, MAPK, and PI3K-Akt signaling pathways along with cholinergic, dopaminergic, serotonergic, glutamatergic synapse, and apoptosis. The docking results suggest that T. cordifolia metabolites could interact with key Alzheimer's disease targets BACE1 and MAO-B, suggesting its role in neuroprotection. These findings provide insights into the biochemical pathways underlying T. cordifolia's therapeutic effects and provides a foundation for future exploration of T. cordifolia in the context of translational research.

PMID:40057579 | DOI:10.1038/s41598-025-92756-5

J Mol Biol. 2025 Mar 7:169046. doi: 10.1016/j.jmb.2025.169046. Online ahead of print.

ABSTRACT

The vast array of cellular ribonucleic acid (RNA) modifications hold a crucial role in regulating RNA stability, folding, localization, and the accuracy of translation. Numerous diseases have been associated with mutations found in genes of RNA-modifying enzymes that can lead to truncated or misfolded proteins incapable of modifying their RNA substrates, causing downstream defects. In contrast, dysregulated levels of RNA-modifying enzymes and the resulting changes in RNA modifications on their substrates are increasingly linked to the activation of oncogenic pathways. This phenomenon has been especially studied through the lens of methyltransferases such as METTL1 and METTL3. The field has developed several small molecule inhibitors of RNA-modifying enzymes to mitigate their related diseases, including targeting the upregulation of METTL3 in cancer. However, increasing evidence suggests that RNA-modifying enzymes play essential roles in numerous cellular processes, including the immune response, neural health, and regeneration, among others. This could lead to off-target effects when treating proteins with small molecules, particularly when these enzymes are upregulated. We propose that developing treatments to specifically target the RNA substrates mis-regulated due to abnormal levels of RNA-modifying enzymes responsible for malignant hallmarks may offer an alternative strategy for treating diseases. We review current RNA-targeted therapies and the diseases they target, including advancements in oligonucleotide modalities and small molecules. We also identify gaps in knowledge that need to be addressed to enhance drug development in the epitranscriptome field to use these therapies to target mis-regulated RNA stemming from altered RNA-modifying enzyme levels.

PMID:40057447 | DOI:10.1016/j.jmb.2025.169046

Int J Biol Macromol. 2025 Mar 6:141823. doi: 10.1016/j.ijbiomac.2025.141823. Online ahead of print.

ABSTRACT

Fungi are widespread organisms with complex multienzyme systems crucial for diverse biochemical processes. This study systematically reviewed research on multienzyme complexes, focusing on their isolation and identification, while examining their potential classification as metabolons. Using a theoretical framework based on PRISMA guidelines, the review analysed literature from 2013 to 2023 across databases such as Medline, Web of Science, and ScienceDirect, employing targeted descriptors to identify relevant studies. The articles were selected by two independent reviewers among those published in English in the last 10 years. From 2313 papers identified through bibliographic searches, 13 were selected for qualitative analysis. Purification methods for fungal multienzyme complexes vary, each offering unique advantages and requiring tailored approaches for specific enzyme systems. The isolation and characterisation of multienzyme complexes face significant challenges. Their classification as metabolons depends on three criteria: substrate channelling, functional coupling, and dynamic assembly. Although research highlights the significance of substrate channelling and the function of stabilising proteins in improving metabolic efficiency, evidence for dynamic assembly is limited. Future research should emphasise new stabilising measures, real-time monitoring of intricate dynamics, and a more profound investigation of molecular causes.

PMID:40057082 | DOI:10.1016/j.ijbiomac.2025.141823