Dalbulus maidis (Hemiptera: Cicadellidae), principal vector of maize stunting pathogens in the Americas, poses a major threat to maize (Zea mays L.) productivity, especially in Argentina. Adult corn leafhoppers exhibit morpho-physiological traits, such as seasonal polyphenism and reproductive quiescence, to withstand unfavorable conditions. However, other physiological responses to seasonal stress remain poorly understood. In this study, we investigated sex-specific metabolic and immunological adjustments that support survival under variable environmental conditions. Adults were field collected during summer, autumn, and winter in Tucumán, Argentina, sexed, and processed for biochemical analysis. For fatty acid profile, adults were classified according to sex and polyphenism (yellow for summer; melanized for autumn/winter). Seasons influenced protein and lipid content, males exhibiting higher protein levels consistently across seasons (438.57 vs 342.87 μg/mg, respectively), and females accumulating more lipids during autumn (59.43 vs 41.91 μg/mg, respectively). Females stored more glycogen than males, particularly in summer (32.70 vs 17.67 μg/mg, respectively) and winter (49.89 vs 10.48 μg/mg, respectively). Phenoloxidase activity showed pronounced sex- and season-dependent variation: females invested in immune activation during colder months (11-17 U/min/mg protein), whereas males maintained consistently low enzymatic activity (6-7 U/min/mg protein). Monounsaturated fatty acids increased whereas polyunsaturated decreased in autumn-winter phenotypes, although the saturated/unsaturated ratio remained similar (0.6-0.7). Females evidenced greater metabolic flexibility and adaptive investment for overwintering, prioritizing energy storage and immune responsiveness, whereas males accumulate resources toward early reproductive efforts. This study provides novel insights into insect physiological plasticity and highlights how environmental stress shapes metabolic and immunological regulation in a major agricultural pest.
The eco-physiological and structural flexibility of Capparis decidua at specific locations along an environmental gradient in the Sargodha region of Pakistan is examined in this work. C. decidua is a xerophyte that thrives in extremely dry and semi-arid environments. Shahpur exhibited the highest electrical conductivity and ionic concentrations (Na⁺ = 29.5 mg kg⁻¹; Cl⁻ = 23.07 mg kg⁻¹) indicating strong salinity stress. The most organic matter (0.83%) was found in Chak 48 NB, which indicates a less harsh environment. There were notable phenotypic differences (p < 0.001) with Shahpur exhibiting greater plant height (139.13 cm), canopy area (3.04 m²), and root length (46.17 cm) associated with saline and drought-prone conditions. Anatomical traits included thicker epidermis (29.5 μm), increased sclerenchyma that are connected to structural elements relating to water conservation. Strong photoprotective mechanisms were suggested by the Shahpur population's stable chlorophyll levels and elevated carotenoid content. PCA biplots showed clear separation of Shahpur from Chak 48 NB and Chak 89 NB along PC1, delineating the Shahpur population and directly correlating it with stress-adaptive anatomical suites. These results suggested that a number of morphological, anatomical, and physiological adaptation features provide a specialized approach to improve drought and salinity tolerance. Further research should focus on molecular pathways and metabolite adaptations for ecological restoration.
This study evaluated the effects of ammonia exposure on the physiological responses, vitality, and histopathology of Pangasianodon hypophthalmus at two temperatures. A 2 × 2 factorial design was applied using two total ammonia nitrogen (TAN) levels (0 and 10 mg/L) and two temperature regimes (28 °C and 32 °C) over a 4-week period. At the end of the experiment, clinical signs, histopathology, hematology, stress indicators (glucose and cortisol), liver function enzymes, and oxidative stress markers (malondialdehyde levels and antioxidant enzymes) were assessed. Fish exposed to 10 mg/L TAN at 32 °C exhibited severe clinical signs, including dermal erosion, muscle necrosis, and respiratory distress. Ammonia exposure at 32 °C significantly reduced red blood cell (RBC) counts, hemoglobin, and hematocrit. Furthermore, elevated temperatures exacerbated ammonia-induced stress, evidenced by significant increases in cortisol, blood glucose, and malondialdehyde levels, alongside altered liver and antioxidant enzyme activities. Histopathological analysis confirmed significant damage to the gill filaments, hepatopancreas, and renal tissues, with severity increasing alongside water temperature. These results indicate a synergistic effect between ammonia exposure and water temperatures, where higher temperatures reduce the threshold for ammonia tolerance, triggering respiratory distress, systemic oxidative stress, and metabolic failure. These findings underscore the critical need for strict water quality management in tropical aquaculture, particularly in regions like Egypt, as rising global temperatures due to climate change may transform currently sub-lethal ammonia levels into potent lethal stressor for P. hypophthalmus. However, the study is limited by controlled laboratory conditions and relatively short experimental duration, suggesting the need for long-term investigations.
Microalgae exhibit remarkable resistance to abiotic stresses, such as salinity. This work investigates the effects of sodium sulfate (Na2SO4) and sodium chloride (NaCl) on the freshwater microalgal strain Chlorella sorokiniana with particular emphasis on physiological activities. The study is focused on understanding the molecular processes of C. sorokiniana in a controlled environment using NaCl and equimolar concentrations of NaCl and Na2SO4. Certain biochemical assays resulted in C. sorokiniana cultured with a salt mixture of 350 mM (NaCl + Na2SO4), showed better growth than 350 mM NaCl. ROS production was high in 350 mM NaCl, which was 1.71 and 1.95 times higher than in the control and in equimolar NaCl + Na2SO4, respectively. The osmolyte level in 350 mM NaCl increased by 2.9 and 2.29-fold as compared to the control and equimolar concentration of NaCl + Na2SO4, respectively. Significant alterations in protein expression suggested that stress-response pathways have been activated. Furthermore, significant fluctuations in osmolyte and antioxidant levels indicate the significant adaptation of the microalgae to salinity stress. These findings contribute to the optimization of microalgae farming by shedding light on the physiological and biochemical strategies of microalgae in saline environments, which are essential to comprehend in order to advance sustainable biotechnological applications.
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Extreme stressor-evoked psychophysiological responses are associated with adverse health outcomes. The present study examined the individual and combined influence of exercise and arousal reappraisal on stressor-evoked psychophysiological responses. Participants (N = 238) were randomly assigned to one of four groups: control (CTRL), arousal reappraisal only (AR), exercise only (EX), or combined arousal reappraisal and exercise (AR + EX). After completing baseline 1, the assigned experimental condition, recovery, and baseline 2, participants underwent a speech task. Cardiovascular measures were obtained during baselines and the stress task, and state psychological measures were obtained after informed consent and after the stress task. Trait reappraisal was also measured. There were no group differences in stressor-evoked cardiovascular responses. However, despite similar stress intensity ratings across all groups, participants in the AR group interpreted their stress more positively. Additionally, moderation analyses demonstrated that individuals with higher trait reappraisal in the EX and AR + EX groups viewed their physiological arousal as more helpful than individuals in the CTRL group. Arousal reappraisal may improve interpretations of acute stress. Additionally, acute exercise may be most beneficial for reducing negative interpretations of perceived physiological arousal when trait reappraisal levels are high. Future research should explore whether repeated arousal reappraisal and exercise training may promote more adaptive stressor-evoked responses.
Adaptive optics retinal imaging (rtx1e, Imagine Eyes, Orsay, France) enables high-resolution visualization of the retinal microvasculature, providing insights into systemic vascular health. Currently, no studies exist describing changes in wall-to-lumen ratio (WLR) during pregnancy, neither during the physiological course of pregnancy nor in pregnancy-associated complications. This single-center, prospective study at the Leipzig University Hospital, Germany, examines changes in retinal microvasculature by employing adaptive optics to calculate the WLR of an arteriole within a few seconds. The study examined a well-phenotyped cohort of 460 primarily White healthy singleton pregnancies, with 543 measurements taken from the first to the third trimester. The WLR was automatically determined using the nnUNet deep learning model. Step-down selection mixed-effects modeling identified gestational week, maternal age, mean arterial pressure, and parity as significant contributors to WLR, whereas body mass index did not improve model fit. In the final model, advancing gestational week (P<0.001), higher maternal age (0.012), and higher mean arterial pressure (<0.001) were independently associated with increased WLR, whereas multiparous women showed significantly lower WLR values compared with nulliparous women, with negligible multicollinearity (variance inflation factor ≈1). We identify WLR as a sensitive marker for imaging microvascular remodeling, serving as an indicator of adaptation to physiological pregnancy. Normal pregnancy is associated with an instant change of the retinal microvasculature indicated by an increase of WLR. Further studies are required to investigate the postpartum course of WLR and establish whether these changes are reversible. URL: https://www.drks.de; Unique identifier: DRKS00032530.
Aging is associated with structural and functional changes of the vocal folds that may result in presbyphonia, often perceived as a weak or shaky voice. However, the quantitative characterization of underlying age-related vocal tremor across the adult lifespan remains limited. This cross-sectional study investigated the characteristics of vocal tremor across the adult lifespan using automated acoustic analysis. A total of 291 native speakers aged 18-94 years were recruited and underwent perceptual voice evaluation and acoustic analysis during sustained phonation of the vowel /a/. Vocal tremor was quantified using digital signal processing, focusing on the prominence of fundamental frequency tremor (PF0T) and the prominence of amplitude tremor (PAT). A moderate-to-strong positive correlation between age and PF0T was observed in both males and females, indicating increasing instability of fundamental frequency with advancing age. In contrast, PAT did not show a significant age-related increase after correction for multiple comparisons. Perceptual ratings of tremor demonstrated only weak correlations with age but were moderately associated with acoustic measures of tremor. Normative models revealed that physiological tremor in healthy aging remains well below pathological thresholds reported in neurological disorders. These findings indicate that age-related vocal tremor is characterized predominantly by increasing instability of fundamental frequency rather than amplitude modulation, localizing the dominant age effect to laryngeal control of vocal fold tension rather than to respiratory drive. Automated acoustic analysis provides a sensitive and objective method for detecting subtle age-related vocal changes and may support future biomarker development for distinguishing physiological from pathological vocal tremor.
Natural Killer (NK) cells are innate lymphoid cells that eliminate malignant cells via perforin/granzyme-mediated cytotoxicity. This study investigates whether Olive Leaf Extract (OLE), rich in oleuropein and hydroxytyrosol, can enhance NK-cell cytotoxicity against colorectal cancer (CRC) cells. Although OLE exhibits direct anticancer effects, its therapeutic utility is constrained by poor bioavailability, requiring supraphysiological concentrations for direct cytotoxicity. To evaluate the effect of OLE on the cytotoxic activity of NK-92 cells against HT-29 colorectal cancer cells within a co-culture model. Olive leaves obtained from Balıkesir, Türkiye were dried and extracted with 70% methanol. The effects of OLE on the viability of HT-29 cells and NK-92 cells were evaluated using MTT and ATP assays. Additionally, the cytotoxic activity of NK-92 cells against HT-29 cells was assessed in a direct co-culture system. Granzyme B and perforin levels were measured using ELISA kits. OLE inhibited the proliferation of HT-29 cells in a dose-dependent manner, with an IC₅₀ values of 548 µg/mL. In NK-92 cells, low concentrations of OLE (100-200 µg/mL) promoted cell proliferation, whereas higher concentrations exerted cytotoxic effects. In co-culture experiments, NK-92-mediated cytotoxicity against HT-29 cells was significantly enhanced by the addition of OLE at non-toxic concentrations (100 and 200 µg/mL). This enhanced cytotoxicity was further supported by a significant increase in granzyme B and perforin levels following OLE treatment. Our findings suggest that OLE can elicit a potent anticancer response via NK cells at lower, physiologically achievable doses. These results highlight a promising therapeutic strategy for CRC, leveraging OLE's immunomodulatory effects to enhance innate antitumor defenses.
To analyze the research dynamics of myopia management functional lenses (MMFL) in the field of vision health over the past decade, revealing cutting-edge hotspots and development trends. Relevant literature on MMFL from 2016 to 2025 in the Web of Science (WOS) core database was searched by computer. The bibliometrics software Bibliometrix, VOSviewer 1.6.20 and CiteSpace.V.6.3.R1 were used for bibliometric and knowledge graph visualisation analyses. A total of 1143 WOS core database documents were included, and the number of publications has gradually increased over time. China and the United States rank the top two in terms of the number of publications and citations. The leading authors in this field are Cho P, Sankaridurg P, and Chen H, who have made significant contributions to research in two distinct subfields: contact lenses and spectacle lenses. Most relevant sources are OPHTHALMIC AND PHYSIOLOGICAL OPTICS, CONTACT LENS & ANTERIOR EYE, and OPTOMETRY AND VISION SCIENCE, all of which are considered to be highly authoritative publications in this field. These journals have published a considerable number of articles on a wide range of topics, including the mechanism of spectacle lenses, physiological changes associated with contact lenses, variations in fitting parameters, and the effects of myopia control. The keywords co-occurrence, clustering, thematic map, timeline view and emergent analyses reveal that recent research has been focused on the following areas: axial length, defocusing mechanism, choroidal thickness, and orthokeratology. The knowledge map of research on MMFL is constructed through bibliometric analysis, systematically summarizing the current status and hotspots of research. The integration of material, optics and intelligence is a trend that is set to be reflected in future functional lenses for myopia management.
Beyond inherited genes and environmentally induced changes in gene expression, phenotypes can also be shaped by parental effects-an effect from a parental phenotype that causes modifications in offspring traits, which cannot be solely explained by the parental or offspring genomes. Such effects may prepare offspring for future environmental conditions and contribute to phenotypic plasticity, including responses to temperature. While temperature-induced plasticity has been extensively studied, the relative contributions of parental versus direct environmental cues remain poorly understood. The fruit fly Drosophila melanogaster is a powerful model for studying physiological and behavioral adaptation to temperature. Flies inhabit environments spanning broad thermal ranges and show evidence of parental effects, such as increased heat tolerance in offspring from warm-reared parents. Here, we exposed mothers to two experimental temperatures and split their broods between the same two temperatures to estimate the relative importance of maternal and developmental effects on adult physiological and developmental responses to temperature. We find that the reaction norms of locomotor activity under gradually increasing temperatures, responses to heat-shock and cold-shock, and fecundity are mostly governed by direct plastic responses to developmental environment. We detected comparatively weak maternal effects in the response to heat-shock, fecundity, and grand-offspring survival where matched environments counteracted the effects of direct offspring experience. We conclude that thermal experience during development is the primary determinant of phenotypic plasticity in D. melanogaster, while maternal experience contributes a small but non-negligible component.
Plants strategically allocate phosphorus (P) among leaf tissues to support physiological functions. However, there is limited understanding of contrasting leaf cellular P-allocation patterns and their physiological consequences. We quantified leaf P fractions, photosynthetic P-use efficiency (PPUE), and P-remobilisation efficiency (PRE) in five chickpea accessions exhibiting contrasting cellular P-allocation patterns. Leaf lifespan and concentrations of key phytohormones were also measured, including abscisic acid (ABA), salicylic acid (SA) and jasmonates. Cellular P-allocation patterns were more strongly associated with leaf lifespan than with PPUE or PRE. Accessions allocating a greater proportion of P to the mesophyll exhibited longer leaf lifespan, which was associated with lower jasmonate concentrations, rather than ABA. Surprisingly, greater P allocation to the epidermis was driven by a higher proportion of metabolite P. At the cellular level, we primarily observed a significant negative correlation between P and calcium concentrations in mesophyll cells, but not in the epidermis. Our findings provide the first evidence that leaf tissue-specific P-allocation patterns vary among chickpea accessions. Preferential allocation of P to photosynthetically active cells was associated with longer leaf lifespan. Differences in jasmonate concentrations accompanied these patterns. Collectively, these findings highlight new opportunities to enhance P-use efficiency in crop breeding programs.
Engineered heart tissues (EHTs) are widely used for cardiac disease modeling and drug screening, but their lack of multicellularity limits translational relevance. Thus, it is essential to incorporate other cardiac cells to improve the reliability and accuracy of the model. To develop a co-culture EHT model from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and cardiac fibroblasts (CFs) and assess its structural, contractile, electrophysiological and metabolic properties. hiPSCs were differentiated into CMs and CFs and combined at a ratio of 3:1 to generate co-culture EHTs. Structural, functional and metabolic features of CM-only and co-culture EHTs were evaluated and compared using immunofluorescence, force analysis, optical mapping and metabolomics. Co-culture EHTs were more compact, generated higher force when stimulated, and displayed improved sarcomere organization compared to CM-only EHTs. They showed reduced hypoxia under high frequency pacing and a more mature, stress resistant metabolic profile, while maintaining stable electrophysiology and reduced arrhythmogenicity. Incorporating hiPSC-CFs into EHTs enhanced structural and functional properties, improved stress resistance, and reduced variability, making our co-culture EHTs a more physiological and predictive platform for cardiac disease modeling and drug screening.
The Small Auxin Up-Regulated RNA (SAUR) gene family has been implicated in various physiological processes in plants, including auxin signaling, senescence, and stress tolerance. Our previous genome-wide transcriptional analyses on postharvest senescence in broccoli (Brassica oleracea L.) identified the BoSAUR gene family as a key regulator in this process. In this study, we examined the expression patterns of BoSAUR family genes under various treatments aimed at delaying postharvest senescence of broccoli, analyzing its protein structure and phylogenetic relationship within the BoSAUR family. We applied gene expression, protein structure, phylogenetic analysis, and mutant characterization to investigate SAUR genes and their roles in senescence. Genome sequences of broccoli were retrieved for identifying BoSAUR genes, followed by phylogenetic, motif, and gene structure analyses using tools like MEME and GSDS. Promoter regions were analyzed with PlantCARE, and chromosomal locations were mapped using TBtools. A T-DNA insertion mutant of SAUR21 gene in Arabidopsis was analyzed for functional analysis. We found that BoSAUR21-like (LOC106327409) was consistently downregulated during natural and postharvest senescence across all treatments, regardless of ethylene status, identifying it as a core senescence-associated gene in broccoli. Genome-wide analysis identified that the BoSAUR21-like gene family shares a single-exon architecture with conserved SAUR motifs. To infer the function of BoSAUR21-like, we characterized the Arabidopsis AtSAUR21 T-DNA insertion mutant, a homologue of BoSAUR21-like. Phenotypic analysis of this mutant revealed accelerated leaf senescence, early bolting, and enhanced chlorophyll degradation compared to wild-type, suggesting that the orthologous BoSAUR21-like gene family likely plays a conserved role in senescence regulation in broccoli. These findings establish BoSAUR21-like gene as a promising candidate for genetic manipulation aimed at delaying postharvest senescence in broccoli and other Brassica crops. Future work should include direct functional characterization of BoSAUR21-like in broccoli through CRISPR-Cas9 knockout and overexpression approaches to confirm its role and assess its potential for extending postharvest shelf life.
The grandmother hypothesis proposes that ancestral women ceased reproduction midlife to instead provision their grandchildren. An alternative "two-sex" account proposes that the high energetic burden of caring for slow-developing offspring was met with biparental investment. Menopause evolved because the physiological costs of reproduction increased with age, yet productivity also increased with age, and the benefits of resource transfers by parents and grandparents of both sexes to adult children and their offspring eventually outweighed the diminishing benefits of continued reproduction. The "father absent" hypothesis proposes that the higher mortality rate of husbands would often have left wives without the resources to raise young children, selecting for early reproductive cessation. Juvenile production plays little role in the three hypotheses, yet subsequent studies have found it to be surprisingly high. Simulations were conducted of hunter-gatherer energy consumption and production across the lifespan, taking account of age- and sex-specific survivorship, interbirth intervals, and varying rates of foraging skill acquisition typical of contemporary foragers. There is a pronounced midlife energy deficit that could be averted with the increasing production of maturing juveniles; midlife cessation of reproduction, which limited the number of mouths to feed; and energy transfers from older parents, and sometimes younger couples (e.g., brideservice). Menopause emerges as an integral and necessary component of the unique human pattern of relatively short interbirth intervals, a long period of juvenile dependency, and extensive food sharing, supporting and extending the "two sex" and grandmother hypotheses.
Carbendazim (CBZ) is a systemic fungicide frequently detected in aquatic environments, where it coexists with multiple pollutants that may alter its toxicity. This study aimed to determine the environmental distribution of CBZ along an upstream-downstream pollution gradient in the Pazarsuyu Stream (Türkiye) and to evaluate its individual and synergistic toxic effects using the Allium cepa bioassay. Surface water samples were collected from five stations representing different agricultural impact zones, and CBZ concentrations were determined using dispersive liquid-liquid microextraction method. Allium bulbs were germinated in these natural water samples and in a laboratory-prepared CBZ solution, and oxidative stress parameters, physiological growth, cytogenetic damage, comet assay endpoints, and meristematic tissue integrity were comprehensively assessed. CBZ concentrations increased progressively from upstream (non-detectable) to downstream (8.53±1.47 ng/mL), confirming cumulative pollution input. Exposure to contaminated water and CBZ alone induced significant oxidative stress, evidenced by increased malondialdehyde, elevated superoxide dismutase and catalase activities, and depletion of glutathione. Comet test results showed that both environmental water samples and CBZ applied at equivalent environmental doses significantly increased DNA damage, but the damage observed in Pazarsuyu samples was higher compared to CBZ alone. Similarly, increases in the frequency of chromosomal abnormalities were found to be more pronounced in environmental samples. This indicates that environmental toxicity stems not only from CBZ but also from synergistic effects with other pollutants. The correlation between spectrally determined DNA destabilization and cytogenetic damage findings reveals that CBZ can directly interact with DNA and disrupt genetic integrity even at environmental doses. Overall, the findings demonstrate that environmentally relevant CBZ concentrations disrupt cellular redox homeostasis, genomic stability, and plant development, and that its ecological risk is substantially amplified in complex environmental matrices. These results emphasize the importance of incorporating synergistic mixture effects into pesticide risk assessment frameworks to better reflect real environmental conditions.
Xylem tissue enables efficient long-distance water transport but is a primary target for vascular pathogens. This study investigates how systemic invasion by Verticillium dahliae impairs the hydraulic function of pepper (Capsicum annuum) plants, focussing on xylem colonisation and its anatomical and physiological effects. Real-time sap flow was continuously monitored with custom-built ExoBeat sensors, while periodic stem water potential measurements allowed calculation of changes in stem hydraulic conductance as an additional indicator of xylem performance. Fungal colonisation was assessed by quantitative polymerase chain reaction, and vessel occlusions and embolised conduits were visualised using scanning electron microscopy and micro-computed tomography, complemented by direct hydraulic conductivity measurements. By 14 d post inoculation, V. dahliae had progressed from roots to aboveground tissues, coinciding with a marked decrease in sap flow, water potential, and soil-to-stem hydraulic conductance, alongside the onset of dwarfing. Direct fungal blockage and anatomical changes were the primary contributors to hydraulic dysfunction. Vessel occlusion by tyloses, gels, and air embolisms played a negligible role. This study reveals how V. dahliae progressively impairs pepper hydraulics through systemic xylem colonisation, highlighting the value of real-time sap flow monitoring. Our integrative, multidisciplinary approach offers a powerful framework to unravel the complexity of dynamic plant-fungal vascular interactions.
This study was designed to inspect the effects of vitamin D3 overdose on the submandibular salivary gland of Albino rats and to investigate the possible protective role of vitamin K1 after one month, as few studies have addressed its histopathological effects. This study was carried out on 60 adult male Albino rats, and they were divided into three groups. Group I (control): received physiological saline. Group II (vitamin D3 overdose): received 1 ml/kg/day cholecalciferol (200 IU) for 30 days. Group III (vitamin D3 + vitamin K1): received the same vitamin D3 dose plus vitamin K1 (15 mg/kg/day) for 30 days. Blood samples were analyzed for baseline and terminal levels of total and ionized calcium. Specimens were examined using Hematoxylin and eosin, alizarin red stain, transmission electron microscopes, and histomorphometric analysis. Statistical analysis was performed using analysis of variance, followed by a post hoc test for pairwise comparisons, and paired t-test for intra-group comparison between baseline and terminal values. examination of group II revealed pronounced structural alterations, notably acinar atrophy, which was statistically validated by a significant reduction in acinar circumference (p-value = 0.024*), alongside ductal degeneration, vascular congestion, and tissue calcification as detected by alizarin red stain. These histopathological changes correlated with elevated serum calcium levels (p-value = 0.001**). In contrast, co-treatment with vitamin K1 in group III substantially mitigated these pathological effects, demonstrating preservation of acinar and ductal structures, attenuation of calcific deposits, and partial normalization of serum calcium levels (p-value = 0.004*). Chronic administration vitamin D₃ overdose triggered degenerative, inflammatory, and calcific changes in the SMG. Also, co-administration of vitamin K1 diminished vitamin D3-induced histopathological changes and hypercalcemia.
The development of far-red light-activatable photolabile protecting groups (PPGs) is crucial for precision medicine applications, yet remains challenging due to the low energy of far-red light photons and the frequent compromise of aqueous solubility. While conditional PPGs activated by specific biochemical conditions offer enhanced spatial control, their scope is limited by the need for external triggers or heterogeneous enzyme expression. Here, we report a new class of dual-responsive PPGs based on a silicon-xanthenium scaffold that are activated by both acidic pH and far-red light. Through systematic structural modification, we developed pcSiR718-OH, a photocage with a low molecular weight (<500 Da) and a red-shifted absorption maximum at 718 nm. pcSiR718CO2H exhibits efficient uncaging (ε × Φuncagingrel = 184 M-1cm-1) under mildly acidic conditions (pH 5.5-6.7) while remaining stable at physiological pH. Mechanistic studies reveal that photolysis can proceed via both homolytic and heterolytic pathways. We demonstrate the utility of this platform through the precise release of bioactive molecules─pomalidomide and gambogic acid─achieving spatiotemporal control over protein degradation in cellular models and tumor growth inhibition in a murine model. This work establishes a versatile strategy for designing environmentally responsive photocages for targeted therapy.
Extracellular vesicles (EVs) are membrane-enclosed structures secreted by virtually all living cells, serving as essential mediators of intercellular communication in both physiological and pathological processes. There is growing interest in their potential applications as biomarkers, therapeutic targets, and drug delivery systems, which entails the need for a detailed understanding of their molecular composition. The functional cargo of EVs includes all types of biological macromolecules, among which proteins are of particular importance. As the vesicular proteome becomes increasingly mapped, research attention is gradually shifting toward post-translational modifications (PTMs), which fundamentally influence protein function and play key roles in all aspects of vesicular activity, including biogenesis, cargo sorting, recognition, and uptake. In this review, we outline recent advances in the application of mass spectrometry (MS)-based analysis of PTMs in EVs. In this context, we provide an overview of the roles of various PTMs in EV biology, discuss the impact of EV isolation methods on downstream PTM analyses, and address current challenges and approaches related to MS-based investigations. We further highlight key findings concerning specific PTMs, including glycosylation, phosphorylation, acetylation, methylation, lipidation, and small ubiquitin-like modifier (SUMOylation). Finally, we discuss studies focusing on the simultaneous analysis of multiple PTMs, as well as efforts toward multiomic data integration and single-EV characterization to resolve vesicular heterogeneity, highlighting these approaches as cutting-edge directions in the field.