J Photochem Photobiol B
· 2026 Mar · PMID 41650633
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Treating biofilm-associated infections is considerably more challenging in the presence of polymicrobial communities comprising bacterial and fungal species. This underscores the need for innovative therapeutic strategie...Treating biofilm-associated infections is considerably more challenging in the presence of polymicrobial communities comprising bacterial and fungal species. This underscores the need for innovative therapeutic strategies. This study evaluated the antimicrobial and immunomodulatory efficacy of carvacrol-loaded bovine serum albumin nanoparticles (CAR@BSANPs) against single- and mixed-species biofilms of Candida tropicalis and Pseudomonas aeruginosa, both alone and in combination with visible light. We assessed antimicrobial photodynamic activity and reactive oxygen species (ROS) production in planktonic cells and biofilms. Then, we validated the results in vivo using a Galleria mellonella infection model. We performed survival analysis, measured haemocyte density, examined immune gene expression, and determined microbial burden. CAR@BSANPs demonstrated strong antimicrobial, antibiofilm, and ROS-generating activities, particularly under visible light exposure. Gene expression analysis revealed downregulation of HWP1, LASR, and PELA, as well as upregulation of TUP1. In vivo, the combined treatment significantly improved larval survival, increased haemocyte density, upregulated gallerimycin and cecropin, and decreased microbial load. Overall, these findings suggest that CAR@BSANPs combined with visible light are an effective nanotherapeutic approach for overcoming biofilm-associated resistance in single- and mixed-species infections.
Neuronal communication relies on neurotransmitter release from synaptic vesicles. The endocytic protein AP180 is critical for efficient vesicle recycling at presynaptic terminals, and its loss impairs neurotransmission,...Neuronal communication relies on neurotransmitter release from synaptic vesicles. The endocytic protein AP180 is critical for efficient vesicle recycling at presynaptic terminals, and its loss impairs neurotransmission, producing reduced release frequency, enlarged synaptic vesicles, and increased quantal amplitude. Yet how AP180 controls vesicle size and whether vesicle size influences release remains unclear. Here, we show that the C-terminal Assembly domain (AD) of AP180 determines vesicle size and thereby regulates release properties in Caenorhabditis elegans. An AP180 variant lacking the AD (AP180∆AD) increases release frequency, contrasting sharply with the reduced transmission in ap180 null mutants, yet fails to correct the vesicle size or quantal amplitude. These enlarged vesicles evade curvature-dependent inhibition by complexin, a presynaptic regulator of fusion, while remaining dependent on complexin for evoked responses. This selective escape reveals that vesicle size influences release dynamics through curvature-sensing proteins. Replacing the AP180 AD with actin-binding motifs restores normal vesicle size, quantal amplitude, and release frequency, indicating that actin interactions are both necessary and sufficient for AD function. Biochemically, we show that the intrinsically disordered AD forms condensates that enrich actin monomers and nucleate filament assembly, while full-length AP180 couples PIP2-rich membranes to actin filaments. Together, these findings reveal that the AP180 AD regulates synaptic vesicle size through actin binding, establishing vesicle morphology as a key influencer of curvature-dependent release control.
J Photochem Photobiol B
· 2026 Mar · PMID 41643631
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Peptide-based photosensitizers (PSs) have emerged as a powerful strategy to overcome the limitations of conventional PSs in photodynamic therapy (PDT), including poor water solubility, low selectivity, and limited photot...Peptide-based photosensitizers (PSs) have emerged as a powerful strategy to overcome the limitations of conventional PSs in photodynamic therapy (PDT), including poor water solubility, low selectivity, and limited phototoxic efficiency. In this study, we synthesized and characterized a novel cinnamoyl-coumarin-RGD peptide conjugate (PS-GG(KG)₃G-RGD), designed to combine tumor-targeting capabilities, improved aqueous solubility, and photodynamic activity modulation by cucurbit[8]uril (CB [8]) complexation. Circular dichroism analysis showed a stable beta-sheet conformation and high-temperature stability for the conjugate. The photophysical behavior of PS-GG(KG)₃G-RGD was evaluated in various solvents, revealing solvent-dependent excited-state dynamics, including the formation of internal charge transfer (ICT) and twisted internal charge transfer (TICT) excited states. Supramolecular complexation with CB[8] resulted in a 1:1 inclusion complex, confirmed by mass spectrometry and Job´s plot; the fluorescence titration showed a high binding constant of (5.0 ± 0.2) × 10 M and stability under acidic conditions. Notably, PS-GG(KG)₃G-RGD binding to CB[8] modulated fluorescence lifetime without significantly altering singlet oxygen generation. In vitro phototoxicity assays in MCF-7 breast cancer cell line demonstrated that the supramolecular assembly significantly enhanced phototoxicity in tumor cells. These findings support the potential of integrating supramolecular approaches with peptide conjugation to photosensitizers as a promising pathway toward the design of novel phototherapeutic agents.
BACKGROUND: G protein-coupled receptors (GPCRs) can signal in the absence of agonists through constitutive activity. This activity can be enhanced by mutations, resulting in receptors known as constitutively active mutan...BACKGROUND: G protein-coupled receptors (GPCRs) can signal in the absence of agonists through constitutive activity. This activity can be enhanced by mutations, resulting in receptors known as constitutively active mutants (CAMs). Such receptors are implicated in various physiological and pathophysiological conditions, and also offer significant therapeutic potential. However, the molecular basis of their constitutive activity remains unknown. RESULTS: To investigate how CAMs affect receptor activation, we employed enhanced sampling simulations to study the dopamine D2 receptor (D2R), a key target in central nervous system therapies. Free energy landscape analyses revealed that CAMs promote a conformational shift favoring an active state similar to the agonist-bound receptor. To then identify novel CAMs, we developed a comprehensive strategy combining structural comparison, in-silico residue scanning, and free energy calculations, validated by luminescence-complementation-based assays. Applied to D2R, this approach uncovered a new single-point CAM, D2R-I48W, which was functionally validated. Further investigation revealed that this mutation activates allosteric communication pathways primarily involving transmembrane helix 5, particularly Ser194, underscoring its role in transmitting activation signals to the intracellular domain. CONCLUSIONS: This study elucidates how CAMs reshape the activation landscape of D2R and establishes a broadly applicable computational-experimental framework for discovering constitutively active GPCR variants. These CAMs provide valuable ligand-independent models for probing receptor activation mechanisms at structural, cellular, and physiological levels.
Biomolecular condensates control key cellular processes, from gene expression to signal transduction, by organizing molecules through selective compartmentalization. Increasing evidence links their dysregulation to cance...Biomolecular condensates control key cellular processes, from gene expression to signal transduction, by organizing molecules through selective compartmentalization. Increasing evidence links their dysregulation to cancer, neurodegeneration, and other diseases, positioning condensates as promising therapeutic targets. This review explores emerging strategies that go beyond dissolving pathological condensates, including approaches that induce, redirect, or reprogram their dynamics, composition, and physical state. Rather than inhibiting individual proteins, these interventions reshape the cellular organization itself. By targeting the material and functional properties of condensates, such strategies offer a new conceptual framework for therapeutic design in complex, dysregulated biological systems.
The clinically significant pathogen Clostridioides difficile lacks the transmembrane nutrient germinant receptors conserved in almost all spore-forming bacteria. Instead, C. difficile initiates spore germination using a...The clinically significant pathogen Clostridioides difficile lacks the transmembrane nutrient germinant receptors conserved in almost all spore-forming bacteria. Instead, C. difficile initiates spore germination using a unique mechanism that requires two signals: a bile acid germinant and a co-germinant, which can be either an amino acid or a divalent cation. While two soluble pseudoproteases, CspC and CspA, were initially identified as the germinant and co-germinant receptors, respectively, in C. difficile, we previously identified residues in an unstructured region of CspC that regulate the sensitivity of C. difficile spores to both signals. However, the mechanism by which CspC transduces these signals remained unclear. Here, we demonstrate that CspC forms a stable complex with CspA and determine the crystal structure of the CspC:CspA heterodimer. The structure reveals extensive interactions along the binding interface, including direct interactions between the unstructured region of CspC and CspA. Using structure-function analyses, we identify CspC:CspA interactions that regulate the sensitivity of C. difficile spores to germinant signals and show that CspA regulates the response of C. difficile to not only co-germinant but also germinant signals. While we show that CspA can form a homodimer and determine its crystal structure, CspA homodimerization appears unimportant for C. difficile spore germination. Collectively, our analyses establish the CspC:CspA heterodimer, rather than its individual constituents, as a critical signaling node for sensing both germinant and co-germinant signals. They also suggest a new mechanistic model for how C. difficile transduces germinant signals, which could guide the development of therapeutics against this important pathogen.
BACKGROUND: Horizontal gene transfer (HGT) is a major driver of microbial evolution, yet the influence of host cellular context on the integration and functionality of transferred genes remains underexplored. In this stu...BACKGROUND: Horizontal gene transfer (HGT) is a major driver of microbial evolution, yet the influence of host cellular context on the integration and functionality of transferred genes remains underexplored. In this study, we investigate how host background impacts the horizontal acquisition of post-translational modification (PTM) machinery. Here, we use heterologous expression of the highly conserved and frequently horizontally transferred translational elongation factor P (EF-P) from diverse species in Escherichia coli as a model. EF-P has a heterogenous relationship with PTMs; three characterized variants each undergo distinct PTM pathways, while others function effectively without any modification. RESULTS: We demonstrate that EF-P from Deinococcus radiodurans, Geoalkalibacter ferrihydriticus, and Nitrosomonas communis can complement an EF-P knockout in E. coli without requiring any PTM, suggesting they may represent new examples of unmodified EF-P. We also found that the EF-P from the Thermotogota Mesotoga prima is post-translationally modified in an off-target reaction by the rhamnosylation enzyme EarP, thus interfering with its functionality. Conversely, we saw that rhamnosylation by EarP does not impact the function of the EF-P-like protein EfpL. CONCLUSIONS: Our findings highlight that PTM systems introduced via HGT can have varied effects on host proteins. We found that different EF-P variants are impacted in different ways by off-target rhamnosylation. While some of these off-target reactions may present opportunities to develop novel, catalytically active PTMs, others are detrimental to the function of the modified EF-P. Our results emphasize the complexity of gene integration and functional compatibility in foreign genomic contexts.
Guo C, Zhang W, Li M
… +4 more, Song C, Zhang X, Wang P, Wang Y
J Photochem Photobiol B
· 2026 Mar · PMID 41616675
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Overexposure to ultraviolet B (UVB) radiation induces oxidative stress, inflammation, and apoptosis, which accelerates collagen degradation and skin aging. Current strategies for managing photodamage mainly focus on sun...Overexposure to ultraviolet B (UVB) radiation induces oxidative stress, inflammation, and apoptosis, which accelerates collagen degradation and skin aging. Current strategies for managing photodamage mainly focus on sun protection and skin repair; however, comprehensive therapeutic approaches are urgently needed. Herbal medicine-derived materials have shown great promise in combating photodamage. Modified Qing'e Formula (MQEF) has demonstrated the ability to treat photodamage by restoring redox homeostasis and is considered an effective anti-photodamage herbal remedy. However, the traditional oral decoction limits its application in topical treatments. In this study, we synthesized novel multifunctional carbon quantum dots (CQDs) using MQEF as a precursor (MQEF-CQDs). These CQDs exhibit superior antioxidant capacity compared to traditional herbal extracts and show no significant toxicity to HaCaT cells, indicating good biocompatibility and potential for skin drug delivery. Furthermore, MQEF-CQDs were incorporated into a thermosensitive hydrogel to form a MQEF-CQDs-hydrogel (MQEF-CQDs-gel) dressing, which is better suited for external use. This hydrogel displays temperature, pH, and rheological properties that align with the skin's physiological environment, along with dual functions of antimicrobial and restorative actions. Both in vitro and in vivo experiments demonstrate that MQEF-CQDs and MQEF-CQDs-gel mitigate UVB-induced photodamage through antioxidant, anti-inflammatory, anti-apoptotic, and collagen degradation-inhibition pathways. Additionally, MQEF-CQDs-gel significantly reduces skin damage, promotes the reconstruction of the epidermal structure, and restores damaged collagen fibers. These findings indicate that MQEF-CQDs represent a promising pathway for the green and sustainable production of herbal-based medicines, with broad industrial applications and as a potent candidate for photodamage treatment.
Zhao P, Jiang Z, He X
… +3 more, Tian T, He F, Ma X
Biology (Basel)
· 2026 Jan · PMID 41594893
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Tibetan sheep, a unique breed indigenous to the Qinghai-Tibet Plateau, exhibit remarkable adaptations to high-altitude hypoxia, and their muscle quality is a key economic determinant. However, the molecular mechanisms by...Tibetan sheep, a unique breed indigenous to the Qinghai-Tibet Plateau, exhibit remarkable adaptations to high-altitude hypoxia, and their muscle quality is a key economic determinant. However, the molecular mechanisms by which exercise regulates meat quality in this breed remain poorly understood. This study aimed to systematically investigate the effects of different exercise volumes on the biceps femoris muscle of Tibetan sheep, integrating histological analysis with high-throughput transcriptome sequencing. We compared a low-exercise group with a high-exercise group and found that long-term endurance exercise resulted in phenotypic changes suggestive of a shift toward oxidative muscle fiber characteristics. This adaptation was characterized by significantly reduced muscle fiber diameter and cross-sectional area, alongside a crucial increase in intramuscular fat content, collectively enhancing meat tenderness, flavor, and juiciness. Transcriptomic analysis revealed extensive gene expression reprogramming, identifying 208 mRNAs and 490 lncRNAs that were differentially expressed and primarily associated with muscle fiber transition and energy metabolism. Furthermore, we constructed a putative lncRNA-miRNA-mRNA competing endogenous RNA network based on expression correlations and bioinformatic predictions, highlighting potential key regulatory axes such as LOC105603384/miR-16-z/, LOC121820630/miR-381-y/, and LOC132659150/oar-miR-329a-3p/. These findings provide a new perspective on the molecular basis of exercise-induced muscle adaptation in high-altitude animals and offer a solid theoretical framework for improving meat quality through scientific livestock management.
Biology (Basel)
· 2026 Jan · PMID 41594891
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CYP3A4 is the main xenobiotic metabolizing enzyme in the human body, as it is in volved in metabolism of ~30% of drugs on the market as well as of many other compounds, from small molecules such as ethanol to large drugs...CYP3A4 is the main xenobiotic metabolizing enzyme in the human body, as it is in volved in metabolism of ~30% of drugs on the market as well as of many other compounds, from small molecules such as ethanol to large drugs such as erythromycin and cyclosporine [...].
BACKGROUND: Cycle of glacial contraction and postglacial expansion in widespread European organisms, as inferred from neutral genetic markers, has led to classic phylogeographic divergence and a primarily latitudinal gra...BACKGROUND: Cycle of glacial contraction and postglacial expansion in widespread European organisms, as inferred from neutral genetic markers, has led to classic phylogeographic divergence and a primarily latitudinal gradient in genetic diversity. However, the relative contribution of adaptive loci, compared to neutral loci, in shaping complex phylogeographic patterns remains poorly understood. RESULTS: We generated extensive genomic datasets for the widespread European species Aquarius najas and its relatives (Aquarius cinereus and Aquarius ventralis), sampled across their entire European distribution. Our results revealed that A. najas is divided into northern and southern lineages, driven in part by major biogeographical barriers in Europe through neutral processes. Additionally, we discovered northern populations exhibiting unexpectedly high genetic diversity, consistent with the cryptic extra-Mediterranean refugia hypothesis. These populations showed evidence of strong, rapid local adaptation, as indicated by the identification of 52 temperature-associated genes (e.g., regulating MAPK thermosensitivity). For the Ibero-Maghrebian populations, our analyses uncovered significant mitochondrial and nuclear introgression from A. cinereus into A. najas. Notably, we identified adaptive introgressed genes, including an ATP-binding cassette (ABC) transporter and the zinc finger protein ZFP91, which likely enhance survival and fitness in the Maghreb region. CONCLUSIONS: Our study presents a comprehensive paradigm for understanding how widespread, limited-dispersal European species adapt to heterogeneous environments through the combined effects of rapid local selection and adaptive introgression, extending beyond the influence of neutral processes alone. Furthermore, we designed and implemented an extended framework for phylogeographic investigation that incorporates both neutral and adaptive dimensions.
BACKGROUND: Anticancer peptides (ACPs) are promising therapeutic agents with selective cytotoxicity toward cancer cells and minimal toxicity toward normal cells. However, the experimental identification and characterizat...BACKGROUND: Anticancer peptides (ACPs) are promising therapeutic agents with selective cytotoxicity toward cancer cells and minimal toxicity toward normal cells. However, the experimental identification and characterization of ACPs are often costly, time-consuming, and inefficient. Computational approaches provide promising alternatives for the rapid and accurate prediction of ACPs. RESULTS: Here, we introduce Aegis, a novel transformer-based deep learning framework designed for precise ACP identification. We systematically evaluated various machine learning and deep learning models via multiple feature extraction methods, including the composition of k-spaced amino acid pairs (CKSAAP), CTD composition (CTDC), CTD transition (CTDT), CTD distribution (CTDD), and pseudo amino acid composition (PAAC) methods. Comprehensive feature importance analyses via analysis of variance (ANOVA), ReliefF, and SHapley Additive exPlanations (SHAP) methods were performed, followed by incremental feature selection (IFS) to determine the optimal subset of discriminative features. Using the 103 optimal features identified via SHAP, Aegis achieves state-of-the-art (SOTA) performance on an independent testing dataset, outperforming existing ACP prediction models. Furthermore, compositional analysis revealed that ACP sequences are significantly enriched in positively charged and hydrophobic residues. CONCLUSIONS: Overall, our study demonstrates the exceptional potential of transformer-based deep learning for ACP identification, laying a foundation for future computational screening and the clinical development of novel ACPs.
Franco MSF, Ravagnani FG, Marie SKN
… +3 more, Oba-Shinjo SM, de Assis LVM, Baptista MS
J Photochem Photobiol B
· 2026 Feb · PMID 41554207
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Photodynamic therapy (PDT) using 1,9-dimethyl methylene blue (DMMB) induces coordinated mitochondrial and lysosomal damage and results in strong cellular death induction. However, the underlying transcriptional regulatio...Photodynamic therapy (PDT) using 1,9-dimethyl methylene blue (DMMB) induces coordinated mitochondrial and lysosomal damage and results in strong cellular death induction. However, the underlying transcriptional regulation in response to DMMB remains elusive. We compared the transcriptome response of photoactivated DMMB (paDMMB) to the gene signature triggered by autophagy-modulating agents: rapamycin (an autophagy activator) and bafilomycin A1 (an autophagy inhibitor). Transcriptome analysis revealed a pronounced transcriptomic response to paDMMB, with 884 differentially expressed genes (DEGs), compared to 291 for bafilomycin and 154 for rapamycin. paDMMB treatment upregulated genes associated with autophagy, mitochondrial stress responses, and proteostasis, while downregulating genes involved in miRNA processing and lipid catabolism. Rapamycin treatment downregulated amino acid biosynthesis pathways, while upregulating processes associated with nutrient starvation. Conversely, bafilomycin treatment upregulated genes related to lipid metabolism, while suppressing cytoskeletal programs. We observed that approximately 80% of bafilomycin DEGs also changed in paDMMB-treated cells, and about 96% of these shared genes showed concordant regulation. This suggests that the paDMMB molecular signature is consistent with the inhibition of autophagic flux. Among the several biological processes affected by paDMMB, mitochondrial-related processes were enriched. To determine whether the acute transcriptome changes caused by paDMMB led to persistent functional effects, we stimulated cells with DMMB and assessed mitochondrial respiration after a recovery period. paDMMB reduced basal respiration, ATP production, proton leak, and maximal respiration. These effects were not further altered by bafilomycin co-treatment but were markedly exacerbated by rapamycin. Collectively, we show that paDMMB leads to a transcriptome rewiring, closely resembling autophagy inhibition with a sustained mitochondrial dysfunction. These findings provide a valuable resource to understand the interplay between DMMB-induced lysosomal stress, transcriptional regulation, and PDT.
Belashov AV, Zhikhoreva AA, Huang Z
… +4 more, Lin F, Semenova IV, Vasyutinskii OS, Qu J
J Photochem Photobiol B
· 2026 Feb · PMID 41547000
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The paper presents time-resolved fluorescence analysis of methylene blue (MB) in solutions and in living cells in vitro. The analysis of MB fluorescence lifetime in solutions of different pH, viscosity and polarity revea...The paper presents time-resolved fluorescence analysis of methylene blue (MB) in solutions and in living cells in vitro. The analysis of MB fluorescence lifetime in solutions of different pH, viscosity and polarity revealed its independence on acidity and viscosity and linear rise with decreasing polarity. Moreover, MB binding to albumin and DNA did not affect its fluorescence lifetime. The obtained dependence of MB fluorescence lifetime on the Lippert-Mataga polarity parameter enabled analysis of polarity distributions in living cells. Fluorescence-lifetime images of MB fluorescence in cancerous HeLa and pseudo-normal bEnd.3 cells provided clear double-exponential signals, which were suggested to be due to diversity of polarity in different cell compartments. The longer fluorescence lifetime and its contribution were shown to differ in cells of different lines, that allowed us to suggest that polarity of low-polar structures and their amount differ in cells of these lines. In cells of both lines the fluorescence lifetimes in nuclei were shorter than those in cytoplasm. The combined analysis of fluorescence lifetimes and phasor plot coordinates allowed for segmentation of the intracellular area to regions of different polarity corresponding to nuclei and cytoplasm with the accuracy of about 90%, and to reveal differences in cells of the two lines.
de Moraes LHO, Sabadini CP, da Silva NF
… +5 more, do Nascimento TA, Buzinari TC, do Couto NF, Phillips SA, Rodrigues GJ
J Photochem Photobiol B
· 2026 Feb · PMID 41546999
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Photobiomodulation (PBM) is a promising non-pharmacological approach to improve vascular function via nitric oxide (NO)-mediated pathways. However, its effectiveness can be limited under conditions of endothelial dysfunc...Photobiomodulation (PBM) is a promising non-pharmacological approach to improve vascular function via nitric oxide (NO)-mediated pathways. However, its effectiveness can be limited under conditions of endothelial dysfunction. This study investigated whether Panax ginseng and Angelica keiskei, two medicinal plants known for their antioxidant and vasorelaxant properties, can enhance PBM-induced vasodilation through mechanisms involving endothelial nitric oxide synthase (eNOS). Aortic rings from Wistar rats were treated with increasing doses of a standardized plant extract combination and exposed to 660 nm laser irradiation. Optimal doses (50-200 mg/kg) significantly potentiated PBM-induced vasodilation, an effect abolished by pharmacological inhibition of NO signaling and endothelium removal. In a chronic eNOS inhibition model (L-NAME), the plant combination did not restore PBM effects but partially recovered acetylcholine-induced vasorelaxation, suggesting endothelial compensation. In mesenteric arteries, the herbal treatment improved acetylcholine sensitivity but did not alter flow-induced or laser-induced vasodilation, especially under hypertensive conditions. These findings highlight a synergistic interaction between phytotherapy and PBM, mediated primarily by eNOS activation and redox modulation, with potential translational relevance for vascular disorders.
Böde K, Sebők-Nagy K, Dlouhý O
… +4 more, Steinbach G, Benda A, Garab G, Páli T
J Photochem Photobiol B
· 2026 Feb · PMID 41544352
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The lipid composition of thylakoid membranes (TMs), the site of light reactions in oxygenic photosynthetic organisms, is dominated by the non-bilayer lipid species monogalactosyldiacylglycerol. It has been documented tha...The lipid composition of thylakoid membranes (TMs), the site of light reactions in oxygenic photosynthetic organisms, is dominated by the non-bilayer lipid species monogalactosyldiacylglycerol. It has been documented that plant TMs display strong lipid polymorphisms (Garab et al. 2022 Prog Lipid Res 86:101163). Recently, we have also shown that BBY membrane sheets, large, laterally fused photosystem-II (PSII) enriched membrane pairs, beside the lamellar phase, contain an intense isotropic phase, the lipid molecules of which mediate the fusion of membranes (Böde et al. 2024 Photosynth Res 161:127-140). To demonstrate the composite nature of BBY, we employed confocal laser scanning microscopy, using the lipid-label BODIPY-phosphatydilcholine and chlorophyll-a fluorescence emissions. To characterize the physico-chemical microenvironments of lipid molecules, we stained BBY membranes with the hydrophobic fluorescent dye DPH (1,6-diphenyl-1,3,5-hexatriene). DPH emission spectra from face- and edge-aligned BBY membranes indicated the existence of at least two distinct microenvironments. Fluorescence lifetime analyses revealed three components; the fastest one was sensitive to the enzymatic treatment with wheat germ lipase (WGL), which had earlier been shown to selectively eliminate the isotropic lipid phase of BBY and to disassemble the large sheets into its constituent membrane pairs of grana. Although the anisotropic fluorescence decay kinetics discerned no lifetime heterogeneity of the untreated DPH-stained BBY, WGL treatment led to the appearance of a second lifetime component. These data provide independent experimental evidence on the lipid polymorphism of BBY membranes and reveal that the bilayer lipids and the non-bilayer lipid arrays mediating the fusion of TMs possess distinct physico-chemical environments.
BACKGROUND: Nematodes communicate via diverse sex pheromones, including long-range volatile signals, short-range chemical cues, and contact-dependent molecules. While the ascaroside family of small molecules that mediate...BACKGROUND: Nematodes communicate via diverse sex pheromones, including long-range volatile signals, short-range chemical cues, and contact-dependent molecules. While the ascaroside family of small molecules that mediate short-range attraction is well characterized, the identities and roles of volatile sex pheromones (VSPs) that act over longer ranges remain unknown. RESULTS: Using GC-MS analysis of crude VSP extracts, we identified cyclohexyl acetate (CA) as a candidate mimic, sharing retention time and mass spectral features with natural VSPs. Behavioral assays demonstrated that CA acts as a concentration-dependent, male-specific attractant in Caenorhabditis. Pre-exposure to VSPs induced cross-adaptation to CA, suggesting shared sensory processing. Surprisingly, genetic and calcium imaging analyses revealed that CA perception is mediated primarily by AWC (str-2-expressing) neurons and involves VSP chemoreceptor srd-1-independent pathways, which are distinct from the neural pathways involved in natural VSP perception. CONCLUSIONS: These data indicate that CA is unlikely to be a major VSP constituent; rather, it is a structural analog that elicits male-specific attraction via a parallel sensory circuit. The endogenous source of CA in C. remanei remains unresolved; our data do not establish whether females produce CA. Its structural and behavioral mimicry provides new insights into the complexity of chemosensory signaling and the potential for interspecies chemical eavesdropping in nematode ecology.
Liu T, Guo B, Tong L
… +8 more, Li H, Wang C, Zang K, Zhao R, Zhao X, Ye C, Ye X, Dang Y
J Photochem Photobiol B
· 2026 Feb · PMID 41539112
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Pearls have skin whitening and antioxidant properties, but their effects on skin barrier are less understood. This study investigated the reparative effects of saccharomyces/pearl ferment lysate filtrate (PFL) on UVB-ind...Pearls have skin whitening and antioxidant properties, but their effects on skin barrier are less understood. This study investigated the reparative effects of saccharomyces/pearl ferment lysate filtrate (PFL) on UVB-induced skin barrier damage. In HaCaT cells, PFL restored proteins related to epidermal differentiation, tight junctions, and moisture retention, all reduced by UVB exposure, and lowered the expression of inflammatory factors. Similarly, in a UVB-induced skin damage mouse model, PFL significantly alleviated skin peeling, erythema, TWEL and epidermal thickening, while also suppressing UVB-induced skin inflammation. Mechanistically, PFL promoted Nrf2 nuclear translocation and upregulated antioxidant proteins NQO1 and HO-1, hereby decreasing ROS accumulation. It also inhibited the activation of the c-Jun N-terminal kinase (JNK) pathway in response to UVB-induced oxidative stress, likely due to the activation of Nrf2. These findings indicate that PFL may repair UVB-induced skin barrier damage through activation of the Nrf2/HO-1 pathway and inhibition of the JNK/MAPK pathway, offering potential as a therapeutic agent for skin barrier repair.
J Photochem Photobiol B
· 2026 Feb · PMID 41520611
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Ultraviolet-C (UV-C) irradiation is a promising approach for inactivating viruses and microorganisms. Germicidal mercury lamps emitting at 254 nm and krypton chloride (KrCl) excimer lamps emitting at 222 nm both possess...Ultraviolet-C (UV-C) irradiation is a promising approach for inactivating viruses and microorganisms. Germicidal mercury lamps emitting at 254 nm and krypton chloride (KrCl) excimer lamps emitting at 222 nm both possess sterilization properties, but the KrCl lamp is considered less harmful to humans. UV-C at 222 and 254 nm induces cyclobutene pyrimidine dimers (CPDs) in Escherichia coli (E. coli). Although E. coli irradiated at 254 nm can undergo photoreactivation, cells exposed to 222 nm cannot, as CPDs are not effectively repaired. This study aimed to investigate the molecular mechanisms underlying bacterial inactivation by UV-C irradiation at 222 and 254 nm. We measured the absorbance of key bacterial components-peptidoglycan (PG), membrane proteins, phospholipids, and DNA-in Gram-negative and Gram-positive bacteria and confirmed the photodecomposition. At 222 nm, a substantial fraction of the light was absorbed by the membrane proteins, and the cleavage of peptide bonds resulted in structural damage and leakage of cellular contents, leading to cell death. In Gram-positive bacteria, which contain thick PG layers, part of the UV-C was absorbed by PG. Irradiation with 222-nm light of PG and proteins resulted in peptide bond cleavage, liberating amino acids. Degradation of the bacterial cell envelope increased the permeability and efflux of intracellular substances, leading to membrane rupture and, ultimately, bacterial cell death. These findings demonstrate that 222-nm irradiation exerts bactericidal effects through distinct mechanisms in Gram-negative and Gram-positive bacteria. SYNOPSIS: The Gram-negative E. coli strain NBRC 106373 and the Gram-positive S. aureus strain NBRC 12732 undergo DNA mutations when irradiated at 222 nm. Simultaneously, they are killed by the leakage of cellular content. This is because the strong light absorption of peptidoglycan and membrane proteins damages the cell structure.
de Alencar BB, de Melo MLFR, Cosme WZ
… +10 more, Dias MHF, Medeiros CCB, Sorrechia R, Pietro RCLR, Silva FG, Andrade E Silva ML, Cunha WR, Pauletti PM, Pires RH, Januário AH
J Photochem Photobiol B
· 2026 Feb · PMID 41518861
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Physalis angulata L. (Solanaceae) is widely recognized for its therapeutic applications in traditional medicine. This study evaluated the antifungal activity of P. angulata (PA) and the influence of red LED-mediated phot...Physalis angulata L. (Solanaceae) is widely recognized for its therapeutic applications in traditional medicine. This study evaluated the antifungal activity of P. angulata (PA) and the influence of red LED-mediated photodynamic therapy (PDT) on planktonic cells and biofilms of Candida albicans, Nakaseomyces glabratus, and Candida parapsilosis. The withanolide 4β-hydroxywithanolide E was isolated from PA, and UPLC-MS analysis of the active fraction (PA-F) in negative ion mode revealed the predominance of eleven withanolides, including aglycone and glycosylated forms belonging to the 5β,6β-epoxide and 5-ene classes. The crude PA extract showed no antifungal activity (MIC >2000 μg/mL) against the tested strains, whereas PA-F exhibited a MIC of 250 μg/mL against C. albicans and 2000 μg/mL against N. glabratus and C. parapsilosis. Notably, exposure of yeast biofilms to PA-F (250 μg/mL) followed by red LED irradiation resulted in a pronounced reduction in viable cells, reaching 4.88 ± 0.12, 4.29 ± 0.15, and 4.16 ± 0.06 log₁₀ CFU/mL for C. albicans, N. glabratus, and C. parapsilosis, respectively, indicating fungicidal activity. These findings demonstrate a light-dependent enhancement of antifungal efficacy, supporting the potential of P. angulata-derived withanolide fractions as photo-responsive agents in antifungal photodynamic strategies.