Popova M, Riabov V, Popova N
… +2 more, Artemiev G, Safonov A
Biology (Basel)
· 2026 May · PMID 42117864
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Radionuclide contamination of surface water bodies poses a significant environmental challenge, particularly for low-productivity dystrophic systems where natural self-purification capacity is limited. This study aimed t...Radionuclide contamination of surface water bodies poses a significant environmental challenge, particularly for low-productivity dystrophic systems where natural self-purification capacity is limited. This study aimed to assess the potential of phytoplankton and bottom sediments as biogeochemical barriers for radionuclides. Laboratory modeling of Sr, U, Pu, and Am accumulation was conducted using samples of Lake Dryazlo (Tver Oblast) water and bottom sediments as a representative dystrophic model system. Sorption onto phytoplankton biomass over a single growing season was estimated at 1.89 × 10, 5.41 × 10, 6.64 × 10, and 4.04 × 10 Bq g dry biomass for Sr, U, Pu, and Am, respectively. Actinide immobilization in bottom sediments depended on mineral composition and microbial community activity. Ammophos addition increased radionuclide removal from the liquid phase by 2-5-fold through enhanced phytoplankton productivity, and promoted actinide fixation via phosphate mineral phase formation and stimulation of anaerobic sulfur- and iron-cycling bacteria. These results demonstrate a viable biogeochemical barrier approach applicable to the decommissioning of radioactive waste storage ponds and remediation of radionuclide-contaminated water bodies.
Qi W, Lü L, Huang K
… +4 more, Qi J, Li M, Shi M, Wang H
Biology (Basel)
· 2026 Apr · PMID 42117813
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The severe continuous cropping obstacles in cultivation, driven primarily by soil microecological imbalance, critically constrain the sustainable development of the industry. To address this challenge, this study evalua...The severe continuous cropping obstacles in cultivation, driven primarily by soil microecological imbalance, critically constrain the sustainable development of the industry. To address this challenge, this study evaluated the efficacy of rotary tillage, calcium cyanamide (CaCN), and organic fertilizer, applied individually and in combination, in mitigating these obstacles and explored the underlying microbial mechanisms. The soil was treated on 5 August 2024, and soil samples were collected on 5 October 2024. Four treatments were established: continuous cropping control (CK), rotary tillage (XGX), rotary tillage combined with calcium cyanamide (MPD), and rotary tillage combined with calcium cyanamide and organic fertilizer (MPX). Soil chemical properties were analyzed in conjunction with metagenomic sequencing to characterize the responses of soil properties and microbial communities, including both eukaryotic and bacterial taxa. The results indicated that the MPD treatment showed a relatively pronounced effect in enhancing key soil fertility indicators, including soil organic matter (OM), total nitrogen (TN), available nitrogen (AN), available potassium (AK), and total phosphorus (TP). All amendments significantly altered microbial community structures. Specifically, the integrated MPX treatment effectively reduced the relative abundance of the pathogenic fungus while maintaining higher overall microbial diversity. It also significantly promoted the abundance of itself and beneficial bacterial phyla such as Actinomycetota and . Redundancy analysis identified AN and AK as the primary drivers of eukaryotic community variation, whereas Availa-ble phosphorus (AP) and potential of hydrogen (pH) were the key factors shaping the bacterial community. The results indicated that MPD was the showed relatively pronounced effectiveness in rapidly improving soil fertility and suppressing pathogenic fungi. In contrast, MPX showed relatively better performance in optimizing microbial community structure, enhancing microbial diversity, and strengthening overall ecological stability. These two treatments exhibited distinct advantages in soil chemical improvement and microbial community regulation, respectively, thereby providing alternative practical strategies and a theoretical basis for the ecological management of continuous-cropping obstacles in cultivation. It should be noted that this study did not include treatments with calcium cyanamide alone, organic fertilizer alone, or their combined application without rotary tillage. This is primarily because rotary tillage is a standard land preparation practice in cultivation, and the use of soil amendments without accompanying tillage is rarely adopted under practical production conditions.
Targeting G-quadruplexes (G4s) presents a promising strategy for cancer therapy, but early-generation ligands often lack tumor selectivity. This study identified X-3, a novel photoactive coumarin-benzothiazolium conjugat...Targeting G-quadruplexes (G4s) presents a promising strategy for cancer therapy, but early-generation ligands often lack tumor selectivity. This study identified X-3, a novel photoactive coumarin-benzothiazolium conjugate, as a dual-targeted photosensitizer against triple-negative breast cancer (TNBC). X-3 localized to both mitochondria and the nucleus, where it specifically bound to mitochondrial and c-Myc G4s with high affinity. Upon light activation, X-3 demonstrated excellent phototoxicity and minimal dark toxicity. Mechanistically, X-3 disrupted mitochondrial bioenergetics by inhibiting mtDNA replication, elevating reactive oxygen species (ROS), and reducing ATP production. Concurrently, it suppressed c-Myc oncogenic expression, shifting the cellular balance toward c-Myc-mediated apoptosis. Validated through 2D and 3D tumor spheroid models, photoactivated X-3 significantly inhibited TNBC proliferation and induced robust cell death. These findings established X-3 as a prototypical, light-controlled anticancer agent integrating molecular targeting precision with photodynamic safety.
Ock CW, Her S, Bae ES
… +3 more, Park HJ, Pyee J, Lee SK
J Photochem Photobiol B
· 2026 Jun · PMID 42102478
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Ultraviolet B (UVB) radiation contributes to skin aging and damage via increasing oxidative stress and mediating inflammatory process in skin. The identification of effective agents to protect UVB-mediated deterioration...Ultraviolet B (UVB) radiation contributes to skin aging and damage via increasing oxidative stress and mediating inflammatory process in skin. The identification of effective agents to protect UVB-mediated deterioration against skin is necessitated. This study aims to examine the protective effects and mechanisms of avenanthramide C (AVN C), a phenolic compound enriched in oat sprout extract (Avena sativa), against UVB-induced photoaging in human keratinocyte cells (HaCaT) and a 3D reconstructed human skin model (Neoderm-ED). AVN C reduced oxidative stress by promoting the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and upregulating antioxidant enzyme expression. AVN C also suppressed the production of inflammatory mediators, including COX-2, IL-1β, and TNF-α, through the inhibition of nuclear factor-kappa B (NF-κB) and upstream MAPK signaling. Moreover, AVN C inhibited UVB-induced matrix metalloproteinase (MMP)-1 and MMP-3 expression, thus preventing extracellular matrix degradation and wrinkle formation. In Neoderm-ED, AVN C protected against UVB-induced structural damage and inflammation by suppressing prostaglandin E production. AVN C exerts an effective anti-photoaging potential by suppression of UVB-induced ROS generation and inflammatory progression. These findings suggest that AVN C may be a promising candidate for anti-photoaging treatment and skin protection.
Lintner M, Golen J, Schagerl M
… +4 more, Wildner M, Wanek W, Cyran N, Tyszka J
J Photochem Photobiol B
· 2026 Jun · PMID 42096980
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Bleaching in symbiont-bearing organisms has been a topic of frequent discussion for years. The most prominent example in the marine environment is coral bleaching, which is associated with the loss of symbionts due to va...Bleaching in symbiont-bearing organisms has been a topic of frequent discussion for years. The most prominent example in the marine environment is coral bleaching, which is associated with the loss of symbionts due to various environmental stressors. Other symbiont-bearing organisms that can be affected by bleaching include Foraminifera (protists). We investigated controlled bleaching in the foraminifera Amphistegina lobifera under laboratory conditions using the menthol/DCMU method to inactivate their obligate photobionts. Specimens were incubated for 35 days and regularly monitored by fluorescence, isotopic uptake, transmission electron microscopy, Pulse-Amplitude-Modulation Fluorometry, and visible and near-infrared spectroscopy. Symbiont metabolic activity decreased steadily with increasing incubation time. Although symbionts were inactive towards the end of the bleaching period, they were neither expelled nor degraded at the subcellular level. Reinoculation of bleached foraminifera with other algae was not possible. Instead, the bleached foraminifera and their original photobionts fully recovered after menthol/DCMU was no longer provided to the culture medium. These results suggest that bleaching cannot be equated to loss of photobionts in A. lobifera. Under the laboratory conditions provided, it is a reversible process, providing positive feedback that bleaching is also reversible under natural conditions if the organisms are only briefly in contact with the disruptive factor.
Ren X, Wang H, Wang K
… +3 more, Mao L, Zhao W, Ren B
J Photochem Photobiol B
· 2026 Jun · PMID 42096979
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Polycystic ovary syndrome (PCOS) stands as a formidable global public health challenge, necessitating advanced diagnostic modalities. Herein, we report the development and multifaceted application of HD-ONOO, an innovati...Polycystic ovary syndrome (PCOS) stands as a formidable global public health challenge, necessitating advanced diagnostic modalities. Herein, we report the development and multifaceted application of HD-ONOO, an innovative hemicyanine-based fluorescent scaffold engineered for the highly selective, real-time monitoring of peroxynitrite (ONOO)-a pivotal reactive oxygen species (ROS) linked to PCOS pathology. Upon site-specific interaction with ONOO, the probe undergoes a structured activation process, yielding pronounced enhancements in both its ratiometric-like absorbance and fluorescence emission profiles. This "turn-on" response demonstrates a robust linear dependency on ONOO concentration, achieving a superior limit of detection (LOD) of 0.03 μM. In vitro assays confirmed that HD-ONOO can faithfully track endogenous ONOO fluctuations, highlighting its utility for early-stage diagnostics and longitudinal disease surveillance. Crucially, clinical validation using PCOS murine models and corresponding serum samples revealed significantly elevated fluorescence intensity compared to healthy cohorts, reinforcing its prognostic value in assessing PCOS risk. Characterized by exceptional chemo-specificity and physiological stability, HD-ONOO represents a versatile analytical platform for non-invasive monitoring and the optimization of early therapeutic interventions in clinical and biomedical research settings.
G protein-coupled receptor 174 (GPR174), a key modulator of autoimmune responses, maintains immune homeostasis through distinct G protein signaling pathways, particularly Gs and Gi. Although the structural mechanism of l...G protein-coupled receptor 174 (GPR174), a key modulator of autoimmune responses, maintains immune homeostasis through distinct G protein signaling pathways, particularly Gs and Gi. Although the structural mechanism of lysophosphatidylserine (LysoPS)-activated GPR174 in the Gs pathway has been characterized, how hydration-mediated interactions influence GPR174 activation and signaling selectivity remains unclear. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of LysoPS-activated human GPR174 bound to Gs (2.0 Å) and Gi (3.4 Å), revealing a continuous hydration-mediated signal transduction network that bridges the sodium-binding pocket, the NPxxY and DRY motifs, and the G protein-binding interface. This network stabilizes the active-state conformation of GPR174 and dynamically reshapes the intracellular cavity, thereby enabling differential engagement of Gs and Gi. Molecular dynamics simulations and functional assays demonstrated that the hydration network is essential for receptor activation and selectively modulates G protein coupling. To evaluate its conservation, we performed sequence alignments and structural analyses across class A GPCRs, defining three hydration cavities: the conserved water cavity (CWC), the junctional water cavity (JWC), and the extended water cavity (EWC), whose hydration is determined by residue properties at position 5.58. Together, our study reveals a hydration-driven molecular mechanism that underlies the activation of GPR174 and its dual G protein selectivity. These findings advance the understanding of hydration-mediated signaling in GPR174 and provide a framework for investigating water-mediated regulation across class A GPCRs.
Li W, Li Z, Zhu H
… +8 more, Wang J, Yuan Y, Zhang K, Wang X, Ni X, Wang J, Hao J, Wang Y
J Photochem Photobiol B
· 2026 Jun · PMID 42085908
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BACKGROUND: Ultraviolet A (UVA) radiation induces skin photoaging. The yeast Clavispora lusitaniae P8, isolated from the Turpan Basin, was studied as a potential source of novel natural anti-photoaging agents. OBJECTIVE:...BACKGROUND: Ultraviolet A (UVA) radiation induces skin photoaging. The yeast Clavispora lusitaniae P8, isolated from the Turpan Basin, was studied as a potential source of novel natural anti-photoaging agents. OBJECTIVE: This study aimed to analyze the composition of its fermented filtrate (P8) and investigate its protective effects and mechanism against UVA-induced damage in human skin cells. METHODS: The chemical profile of P8 was analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS). Optimal UVA dose and a protective P8 concentration were determined by MTT assay. In HaCaT and HFF-1 cells, protective effects were evaluated by measuring markers including Lactate Dehydrogenase (LDH) release, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cell migration, malondialdehyde (MDA), and antioxidant enzyme activities. RESULTS: P8 contained photoaging-related compounds (carboxylic acids and derivatives, organooxygen compounds, fatty acyls, and flavonoids) and significantly alleviated UVA-induced cellular damage by reducing oxidative stress markers, restoring mitochondrial function, promoting cell migration, increasing type I collagen levels, and suppressing matrix metalloproteinases expression. Transcriptomic and metabolomic analyses identified the Interleukin-17 (IL-17) signaling pathway as the key pathway. Western blotting confirmed that P8 inhibited UVA-induced activation of the IL-17 pathway, reducing expression of interleukin-17 receptor A (IL-17RA) and phosphorylated nuclear factor kappa B (p-NF-κB). Furthermore, using the IL-17 A neutralizing antibody Ixekizumab verified that the anti-photoaging effect is primarily mediated through the IL-17 A/NF-κB axis. CONCLUSION: This study is the first to link P8 with the inhibition of the IL-17/NF-κB axis, confirming its potential as a promising anti-photoaging candidate.
BACKGROUND: Early-branching metazoans, such as sponges (Porifera), can provide valuable insight into the emergence of complex gene regulatory systems and cancer-related mechanisms in early metazoan evolution. BRMS1 (brea...BACKGROUND: Early-branching metazoans, such as sponges (Porifera), can provide valuable insight into the emergence of complex gene regulatory systems and cancer-related mechanisms in early metazoan evolution. BRMS1 (breast cancer metastasis suppressor 1) is a component of the Sin3-HDAC complex involved in chromatin remodeling and transcriptional regulation. In humans, BRMS1 inhibits cancer metastasis by modulating signaling pathways that control cell migration, adhesion, and proliferation. Despite its biomedical importance, the evolutionary origin and basic functions of BRMS1 remain largely unexplored. RESULTS: We identified and characterized a BRMS1 homolog from the cave sponge Eunapius subterraneus and compared it with human BRMS1 and BRMS1-like paralogs. Phylogenetic analyses revealed that BRMS1 and BRMS1-like arose from a duplication of an ancestral BRMS1 gene during early vertebrate evolution. Structural modeling showed that sponge BRMS1 shares high similarity with human BRMS1. Co-immunoprecipitation assays demonstrated that sponge BRMS1 physically associates with human BRMS1 in mammalian cells. In both sponge and human cells, sponge BRMS1 localized predominantly to the nucleus, similar to human BRMS1 and BRMS1-like. Functional assays in human breast cancer cells revealed that sponge BRMS1 suppresses proliferation, colony formation, and migration to a degree comparable to its human homologs. CONCLUSIONS: Our findings demonstrate that the key structural features, subcellular localization, and biological functions of BRMS1 are conserved between sponges and humans. The ability of a sponge BRMS1 homolog to integrate into human protein complexes and suppress cancer cell migration and proliferation suggests that fundamental BRMS1 activities arose early in metazoan evolution, independent of anatomical and functional complexity.
Deeva AA, Lisitsa AE, Lyapina AK
… +3 more, Kratasyuk VA, Murugan NA, Nemtseva EV
J Photochem Photobiol B
· 2026 Jun · PMID 42070364
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Bacterial luciferase is a member of the large family of flavin monooxygenases, among which it performs the unique bioluminescent reaction. We studied the interaction of two bacterial luciferases (Vibrio harveyi - of "slo...Bacterial luciferase is a member of the large family of flavin monooxygenases, among which it performs the unique bioluminescent reaction. We studied the interaction of two bacterial luciferases (Vibrio harveyi - of "slow" type and Photobacterium leiognathi - of "fast" type) with aliphatic aldehydes using experimental kinetic techniques, molecular docking, molecular dynamics and phylogenetic analysis. The aim was to understand the structural basis for the different kinetic properties of the two types of luciferase with aldehyde substrate. We found that a distinctive feature of the active site of V. harveyi luciferase was the presence of a minor aldehyde-binding pocket. In P. leiognathi luciferase, all aldehydes bound to the hydrophobic site of the active center in approximately the same conformation, differing only in the binding affinity. In V. harveyi luciferase, aldehydes C and C did not interact with αTrp194, consistent with their slow reaction kinetics. The molecular dynamics and free energy calculations indicated that the hydrophobic interaction between the aldehyde and protein is the driving force for the complex stability. Phylogenetic analysis of bacterial luciferase sequences revealed that amino acids from the aldehyde binding site at positions 6-8, 191-195, and 228-229 are under positive evolutionary selection. These data indicate that evolutionary processes have shaped a universal platform for binding the natural aldehyde tetradecanal, enabling efficient catalysis in both "fast" and "slow" luciferases. However, when shorter aldehydes are used in bioluminescent assays, the specific features of their interactions within the active site must be taken into account, as they determine the kinetics of the enzyme.
Dimmer J, Campagno L, Comin R
… +4 more, Rivarola W, Petenatti E, Tempesti TC, Funes MD
J Photochem Photobiol B
· 2026 Jun · PMID 42066647
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Cutaneous leishmaniasis (CL) is a neglected tropical disease with limited therapeutic options due to toxicity, resistance, and high costs. Photodynamic therapy offers a promising alternative; however, the systematic eval...Cutaneous leishmaniasis (CL) is a neglected tropical disease with limited therapeutic options due to toxicity, resistance, and high costs. Photodynamic therapy offers a promising alternative; however, the systematic evaluation of furanocoumarin-rich plant extracts in Leishmania models remains limited. Despite the well-established photodynamic properties of individual furanocoumarins, no systematic evaluation of Trichocline plicata extracts has been performed in protozoan parasites. This study aimed to provide an integrated evaluation of the chemical composition, intrinsic photophysical properties, and biological photodynamic efficacy of furanocoumarin-rich extracts from Trichocline plicata against Leishmania amazonensis. Extracts from aerial and subterranean parts were chemically characterized by UHPLC-DAD and GC-MS, and their photodynamic potential was assessed through singlet oxygen and superoxide anion radical generation under UVA irradiation. Antiparasitic activity was tested in vitro, and morphological alterations were examined by optical and scanning electron microscopy, while cytotoxicity was evaluated in Vero cells. The dichloromethane extract from subterranean parts (DCM-SP.Ext.) showed the highest production of singlet oxygen and superoxide anion radical. Photodynamic treatment reduced parasite viability by up to 97%, comparable to amphotericin B, and microscopy revealed severe morphological damage in irradiated parasites. Mechanistic analyses using ROS quenchers and anoxic conditions demonstrated that both oxygen-dependent (Type I/II) and oxygen-independent (Type III) pathways contribute to parasite inactivation, supporting a multimodal photodynamic mechanism. DCM-SP.Ext. exhibited low toxicity in Vero cells, suggesting high selectivity toward the parasite. These findings establish T. plicata extracts, particularly DCM-SP.Ext., as efficient and selective natural photosensitizers capable of inducing multiple photodynamic mechanisms, supporting their potential as cost-effective plant-based agents for the photodynamic treatment of cutaneous leishmaniasis. This work highlights the potential of native plants as renewable sources of bioactive compounds for photodynamic applications in infectious diseases.
Uncovering what drives select biomolecules to form phase-separated condensates in vivo and identifying their physiological significance are topics of fundamental importance. Here, we show that nitrogen-starved Escherichi...Uncovering what drives select biomolecules to form phase-separated condensates in vivo and identifying their physiological significance are topics of fundamental importance. Here, we show that nitrogen-starved Escherichia coli produces long-chain polyphosphates, which scaffold the RNA chaperone Hfq into high molecular weight complexes, which eventually phase separate together with components of the RNA translation and processing machinery. The presence of polyphosphate within these condensates controls Hfq function by selectively stabilizing polyadenylated RNAs involved in transcription and protein translation and by promoting interactions with translation- and RNA-metabolism-associated proteins involved in de novo protein synthesis. Lack of polyphosphate significantly impairs condensate formation, increases cell death, and hinders recovery from N-starvation. In functional analogy, we demonstrate that polyP contributes specifically to the formation of Processing (P)-bodies in mammalian cell lines, revealing that a single, highly conserved and ancestral polyanion serves as a modulator for functional phase-separated condensate formation across the tree of life.
Termites produce the most diverse array of terpenoids among terrestrial metazoans, comprising over 200 structures. However, their biosynthesis has not yet been elucidated. Here, we identify a gene family which arose thro...Termites produce the most diverse array of terpenoids among terrestrial metazoans, comprising over 200 structures. However, their biosynthesis has not yet been elucidated. Here, we identify a gene family which arose through a series of duplications of geranylgeranyl pyrophosphate synthase in the common ancestor of Neoisoptera, the terpene-producing termite lineage. We functionally characterized several proteins from this rich GGPPS-like family as terpene synthases generating biologically relevant sesqui- and diterpenes. These include the queen pheromone (3R,6E)-nerolidol in Embiratermes neotenicus and the presumed precursor of polycyclic defensive diterpenes (E,E,E)-neocembrene in Nasutitermes takasagoensis. We report significant enrichment of transposable elements in the GGPPS-like genomic loci, study the selection pressures acting in the evolution of the GGPPS-like family, and highlight an amino acid site crucial for cyclization capacity and enantiospecificity of the characterized enzymes. We conclude that we have identified an enzyme family that facilitated the emergence of the remarkable richness of termite terpenoids.
Biology (Basel)
· 2026 Apr · PMID 42041940
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Dietary habits are pivotal in preventing chronic noncommunicable diseases, as vegetable-rich diets provide over 25,000 bioactive phytochemicals that modulate cell-signaling and metabolic pathways. Consequently, nutraceut...Dietary habits are pivotal in preventing chronic noncommunicable diseases, as vegetable-rich diets provide over 25,000 bioactive phytochemicals that modulate cell-signaling and metabolic pathways. Consequently, nutraceuticals and functional foods are increasingly recognized for their potential to prevent chronic pathologies. Among functional foods, L. (common bean) stands out as a critical resource for global nutrition and disease prevention. Beyond its role in food security and environmental sustainability, the common bean offers extraordinary nutrient density, providing a unique "protein plus fiber" package and a source of health-promoting active ingredients. In this review, special emphasis is placed on the bean's role in preventing or mitigating cardiovascular diseases and cancer, driven by bioactive molecules that modulate metabolic and cell-signaling pathways. Practical evidence of this growing interest is demonstrated by the surge in scientific literature over the last 50 years, as shown by PubMed and Scopus data. By synthesizing data from original research and existing reviews, this work highlights how incorporating common beans into the diet represents a strategic, health-conscious choice with potential therapeutic benefits for human health.
Biology (Basel)
· 2026 Apr · PMID 42041910
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Natural products (NPs) have historically provided the foundational scaffolds for drug development, yet traditional bioprospecting faces critical limitations: high rediscovery rates, laborious isolation workflows, and sub...Natural products (NPs) have historically provided the foundational scaffolds for drug development, yet traditional bioprospecting faces critical limitations: high rediscovery rates, laborious isolation workflows, and substantial attrition during clinical translation. The emergence of big data technologies is fundamentally transforming this landscape, enabling a shift from serendipity-based discovery toward systematic, data-driven approaches. This review examines how the integration of artificial intelligence (AI), machine learning (ML), and multi-omics datasets is accelerating natural product research across three key domains: (1) genome mining for biosynthetic gene cluster identification using platforms such as antiSMASH, (2) cheminformatics-driven prediction of structure-activity relationships and ADMET properties, and (3) metabolomics-guided dereplication to prioritize novel bioactive scaffolds. We evaluate the convergence of genomics, metabolomics, and computational chemistry in enabling lead optimization and the discovery of cryptic metabolites from previously inaccessible microbial taxa. While challenges in data standardization and scalability persist, the synergy between big data and NP research is accelerating clinical translation. Despite persistent challenges in data standardization, scalability, and equitable benefit-sharing, the convergence of big data and NP research is poised to redefine drug development. These advances position computational NP research as a cornerstone of next-generation drug development.
Alves THO, Silva JR, Limeira IM
… +2 more, Rhein S, Souza AO
Biology (Basel)
· 2026 Apr · PMID 42041885
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Modern lifestyles characterized by reduced physical activity and changing eating habits have contributed to a global rise in obesity. This research examined the effects of a diet rich in linoleic acid combined with physi...Modern lifestyles characterized by reduced physical activity and changing eating habits have contributed to a global rise in obesity. This research examined the effects of a diet rich in linoleic acid combined with physical exercise using a TreadWheel system in . The flies were fed diets with varying linoleic acid concentrations from the larval stage through to day 15 of adulthood. A diet containing 45.9 mg/mL of linoleic acid improved eclosion rates, body weight, and biochemical markers such as glycogen, cholesterol, and hydrogen peroxide levels, as well as citrate synthase and acetylcholinesterase activities in sedentary flies. Conversely, flies that consumed linoleic acid and underwent 15 days of exercise on the TreadWheel showed increased weight, lactate, glycogen, cholesterol, nitric oxide levels, and acetylcholinesterase activity. These results suggest that a 15-day regimen of linoleic acid intake combined with physical exercise on the TreadWheel enhances muscle parameters in , serving as an alternative animal model for nutrition and exercise research.
Xie Y, Sun Y, Li X
… +6 more, Zheng L, Wang Y, Xu C, Zhang L, Yu B, Zhu L
J Photochem Photobiol B
· 2026 Jun · PMID 42033853
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Superficial mucosal and skin infections caused by Candida albicans remain a clinical burden because current antifungals rarely combine high potency with host safety. Here, we report berberine (BBR)-derived aggregation-in...Superficial mucosal and skin infections caused by Candida albicans remain a clinical burden because current antifungals rarely combine high potency with host safety. Here, we report berberine (BBR)-derived aggregation-induced emission (AIE) photosensitizers for photodynamic therapy (PDT), in which alkyl-chain length is tuned to modulate molecular amphiphilicity, nanoaggregation, and fungal selectivity. A series of cationic AIE derivatives (CABs) was constructed and evaluated for antifungal activity and biocompatibility. Upon 405 nm irradiation, CABs efficiently generated reactive oxygen species through both Type I and Type II photodynamic pathways, including HO• and O₂. In vitro, the medium-chain derivative CAB-8 showed a favorable balance between uptake and cytocompatibility: under 405 nm irradiation, CAB-8 achieved nearly 99.9% fungicidal killing against C. albicans and outperformed fluconazole, while displaying preferential uptake by fungal over mammalian cells, consistent with reduced host phototoxicity. Transcriptomic profiling revealed a dual intrinsic antifungal mechanism under dark conditions, involving concomitant disruption of mitochondrial oxidative phosphorylation and ribosome-dependent protein synthesis. In vivo, CAB-8-mediated PDT enhanced fungal clearance and wound healing in a skin burn infection model and prevented C. albicans colonization in an oral mucosal infection model, without evidence of systemic toxicity. These findings establish alkyl-chain engineering of BBR-based AIE photosensitizers as an effective strategy to improve the efficacy-safety profile of PDT for localized treatment and prevention of superficial C. albicans infections.
J Photochem Photobiol B
· 2026 Jun · PMID 42019119
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In the concerted efforts to advance the understanding of oxidative stress and its impact, study was conducted to explore the influence of iodide on the anoxic photo-oxidation of model peptide - Met-enkephalin. The time-r...In the concerted efforts to advance the understanding of oxidative stress and its impact, study was conducted to explore the influence of iodide on the anoxic photo-oxidation of model peptide - Met-enkephalin. The time-resolved experimental results indicated the quenching of 3CB* by electron transfer, yielding mainly TyrO, together with 3CB and 3CBH. The addition of iodide induced a competitive reaction (with iodide acting as an additional quencher), which shortened the lifetime of 3CB*. Stable products resulting from the oxidation of MetEnk by 3CB* complements previous works on MetEnk irradiations, showing formation of products on Met and Tyr side chains (CBH-adducts to Met and diTyr). The presence of iodide anions protected the MetEnk from oxidation due to competitive quenching of 3CB* and no new products have been identified as the action of iodide anions.
P2X receptors are ATP-gated cation channels, and the P2X3 subtype plays crucial roles in peripheral sensory neurons, including in chronic pain and chronic cough. Accordingly, P2X3 receptors have attracted substantial int...P2X receptors are ATP-gated cation channels, and the P2X3 subtype plays crucial roles in peripheral sensory neurons, including in chronic pain and chronic cough. Accordingly, P2X3 receptors have attracted substantial interest as a therapeutic target. Gefapixant, a negative allosteric modulator (NAM) of P2X3 receptors, has been approved in some countries for the treatment of chronic cough; however, its limited selectivity for P2X3 homomers over P2X2/P2X3 heteromers is associated with taste disturbance as a prominent adverse effect. These limitations have motivated the development of next-generation NAMs with improved subtype selectivity, but their subtype-specific allosteric inhibition mechanisms are unclear. Here, we report the cryo-EM structure of the human P2X3 receptor in complex with ATP and the P2X3-selective next-generation NAM sivopixant, an investigational drug. Sivopixant binds to an allosteric site at the portal of the central pocket in the extracellular domain, and structure-based mutational analysis by electrophysiology identifies key residues required for sivopixant-dependent inhibition of human P2X3 receptors. Structural comparisons across P2X subtypes, together with patch-clamp analyses of gain-of-function mutants that confer sensitivity to two investigational drugs, sivopixant and camlipixant, provided a broadly applicable structural framework for subtype selectivity. Furthermore, structural comparisons with apo and ATP-bound open states of P2X3 receptors, together with molecular dynamics simulations, revealed that sivopixant expands the upper-body domain to suppress the lower-body movements required for channel activation, thereby preventing channel opening even in the presence of ATP.
Biological clocks shape metabolism, but how circadian programs govern nutrient processing is unclear. Here, using human metabolomics and 13C6-glucose tracing in Drosophila, we delineate previously under characterized dai...Biological clocks shape metabolism, but how circadian programs govern nutrient processing is unclear. Here, using human metabolomics and 13C6-glucose tracing in Drosophila, we delineate previously under characterized daily oscillations in glucose-derived metabolic networks, providing a mechanistic framework for a purpose-built isotope-tracing approach. In flies, we reveal a pronounced "rush hour" of glucose utilization early in the light phase, with carbons directed to biosynthetic and energetic pathways. By contrast, a dopamine reuptake-deficient hyperactive mutant (fumin) with elevated metabolic rate shows phase-shifted and amplified metabolic peaks, indicating that altered neural signaling reshapes temporal glucose flux. Neither altered feeding schedules nor short-term fasting disrupt these intrinsic metabolic rhythms, strongly suggesting that circadian timing, rather than nutrient availability, orchestrates temporal homeostasis. By integrating human metabolite profiling with isotope-tracing in flies, we define a conserved temporal architecture of glucose utilization and demonstrate that metabolic flux is dynamically gated across the day. Our findings establish a framework for understanding how circadian misalignment contributes to metabolic dysfunction and disease.