Search Results (163)

Leaf senescence is a developmental process that allows nutrients to be remobilized and transported to sink organs. Previously, papain-like cysteine proteases (PLCPs) have been found to be highly expressed during leaf senescence in different plant species. In this study, we analyzed active PLCPs in barley (Hordeum vulgare L.) leaves during the terminal stage of natural senescence. Anion exchange chromatography of protein extracts from barley leaves, harvested six weeks after anthesis, followed by activity assays using the substrates Z-FR-AMC and Z-RR-AMC, revealed a single prominent peak corresponding to active PLCPs. This hydrolytic activity was completely inhibited by E-64, a potent and irreversible inhibitor of cysteine proteases. Fractions enriched for PLCP activity were affinity-labeled with DCG-04 and subjected to SDS-PAGE fractionation, separating two major bands at 43 and 38 kDa. These bands were analyzed using tandem mass spectrometry, allowing the identification of eleven PLCPs. Identified enzymes belong to eight PLCP subfamilies, including CTB/cathepsin B-like (HvPap-19 and -20), RD19/cathepsin F-like (HvPap-1), ALP/cathepsin H-like (HvPap-12 or aleurain), SAG12/cathepsin L-like A (HvPap-17), CEP/cathepsin L-like B (HvPap-14), RD21/cathepsin L-like D (HvPap-6 and -7), cathepsin L-like E (HvPap-13 and -16), and XBCP3 (HvPap-8). Among the identified PLCPs, HvPap-6 was the most abundant. Peptides corresponding to HvPap-6 were identified in both the 43 kDa and 38 kDa bands in approximately the same quantity based on total spectral count. Thus, our results indicate that two active HvPap-6 isoforms can be isolated from barley leaves at late senescence. Full article

Anthracyclines are widely used chemotherapeutic agents with proven efficacy against a broad range of malignancies, but their clinical utility is limited by a well-documented, dose-dependent cardiotoxicity. While this toxicity has traditionally been attributed to direct cardiomyocyte injury, emerging evidence highlights the pivotal role of cardiac fibroblasts (CFs) in the development and progression of anthracycline-induced cardiotoxicity. This review examines the diverse effects of anthracycline focusing on doxorubicin (DOX) and CFs across the temporal phases of cardiac injury. DOX activates fibroblast-driven extracellular matrix remodeling and promotes fibrosis through enhanced collagen production and the induction of cellular senescence, thereby exacerbating early myocardial inflammation and dysfunction. Clinically, anthracycline cardiotoxicity may present as acute (within days), subacute (within weeks), or chronic progressive forms manifesting either early (within one year) or late (up to decades post-treatment). While early manifestations may be reversible with timely detection and management, late-phase cardiotoxicity is often irreversible, characterized by declining left ventricular ejection fraction and heart failure. A deeper understanding of the molecular and cellular contributions of CFs may uncover novel therapeutic targets to prevent or attenuate anthracycline-related cardiac damage. Full article

Leaf senescence, the terminal phase of leaf development, is governed by transcription factor (TF)-mediated genetic reprogramming events that significantly impact plant physiology and productivity. While TF-mediated senescence regulation has been demonstrated in various plant species, the underlying molecular mechanisms remain incompletely understood. This study investigated the regulatory roles of NAC family TFs in leaf senescence using two Clerodendrum japonicum lines exhibiting contrasting senescence phenotypes. Through integrated transcriptome sequencing, weighted gene co-expression network analysis (WGCNA), and functional enrichment approaches, we systematically analyzed temporal gene expression patterns during leaf senescence. Phenotypic characterization revealed distinct chlorophyll degradation dynamics between the lines, quantified by SPAD values. Transcriptomic analysis identified 232 consistently differentially expressed genes (DEGs) across senescence stages, among which 193 were annotated as NAC transcription factors. WGCNA delineated senescence-associated gene modules, with the turquoise and darkred modules showing particularly strong correlations with senescence progression. Further investigation identified 25 NAC genes exhibiting stage-specific expression patterns, and functional analysis revealed that 15 of these were significantly enriched in organ senescence-related pathways. qRT-PCR validation confirmed that the four core NAC regulators showed up to 5-fold higher expression in the early-senescing line during late senescence stages. These findings delineate the NAC-mediated regulatory network governing leaf senescence in C. japonicum, offering potential molecular targets for manipulating senescence progression, which warrants further functional characterization and practical application in plant improvement. Full article

Background: Generalized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies. Objective: This review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes. Methods: A narrative review was conducted, integrating recent findings from clinical trials, immunogenetic studies, and preclinical research to describe subtype-specific immune mechanisms and corresponding therapeutic innovations. Results: gMG subtypes—characterized by autoantibody profiles (AChR, MuSK, LRP4, or seronegative), thymic histopathology, and age of onset—demonstrate distinct immunological pathways. Early-onset MG is associated with thymic hyperplasia and Th17-driven inflammation; thymoma-associated MG involves central tolerance breakdown; late-onset MG shows immune senescence and altered T-cell regulation. MuSK- and LRP4-positive MG exhibit unique cytokine and antibody signatures. Novel therapeutic strategies include B cell- and T cell-targeted therapies (e.g., anti-CD19, anti-CD38, JAK inhibitors), cytokine inhibitors (IL-6, IL-17, IL-23), FcRn antagonists, complement inhibitors, and gene- or cell-based therapies such as CAR-T and CAAR-T cells. Conclusion: The evolving landscape of gMG treatment reflects a shift toward immunopathology-based precision medicine. Better characterization of subtype-specific molecular signatures and immune dysfunctions is essential to guide clinical decision-making and improve outcomes for treatment-refractory patients. Full article

The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca²⁺-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article

Sporadic Parkinson’s Disease (PD) affects 3% of people over 65 years of age. People are living longer, thanks in large part to improvements in global health technology and health access for non-neurological diseases. Consequently, neurological diseases of senescence, such as PD, are representing an ever-increasing share of global disease burden. There is an intensifying research focus on the processes that underlie these conditions in the hope that neurological decay may be arrested at the earliest time point. The concept of neuronal death linked to ageing- neural senescence- first emerged in the 1800s. By the late 20th century, it was recognized that neurodegeneration was common to all ageing human brains, but in most cases, this process did not lead to clinical disease during life. Conditions such as PD are the result of accelerated neurodegeneration in particular brain foci. In the case of PD, degeneration of the substantia nigra pars compacta (SNpc) is especially implicated. Why neural degeneration accelerates in these particular regions remains a point of contention, though current evidence implicates a complex interplay between a vast array of neuronal cell functions, bioenergetic failure, and a dysfunctional brain immunological response. Their complexity is a considerable barrier to disease modification trials, which seek to intercept these maladaptive cell processes. This paper reviews current evidence in the domain of neurodegeneration in Parkinson’s disease, focusing on alpha-synuclein accumulation and deposition and the role of oxidative stress and inflammation in progressive brain changes. Recent approaches to disease modification are discussed, including the prevention or reversal of alpha-synuclein accumulation and deposition, modification of oxidative stress, alteration of maladaptive innate immune processes and reactive cascades, and regeneration of lost neurons using stem cells and growth factors. The limitations of past research methodologies are interrogated, including the difficulty of recruiting patients in the clinically quiescent prodromal phase of sporadic Parkinson’s disease. Recommendations are provided for future studies seeking to identify novel therapeutics with disease-modifying properties. Full article

Black rockfish (Sebastes schlegelii) is a marine ovoviviparous teleost that exhibits significant sexual dimorphism, with females growing faster and reaching larger sizes than males. Establishing stable oogonial stem cells (OSCs) is critical for understanding germline stem cell dynamics and facilitating all-female breeding. In this study, we successfully isolated and cultured OSCs from S. schlegelii for 12 passages. These cells exhibited alkaline phosphatase activity, expressed germline marker genes (ddx4, cdh1, klf4), and maintained a diploid karyotype (2n = 48). Transcriptomic comparisons between early (P3) and late (P12) passages revealed significant metabolic dysfunction and cell cycle arrest in the late-passage cells. Specifically, the down-regulation of glutathione-related and glycolysis-related genes (gstm3, gstt1, mgst3, gsta1, gsta4, gsto1, gapdh) and key mitotic regulators (cdk1, chk1, cdk4, e2f3, ccne2, ccnb1) suggested that metabolic imbalance contributes to oxidative stress, resulting in cell cycle inhibition and eventual senescence. This study provides a marine fish model for investigating metabolism-cell cycle interactions in germline stem cells and lays the foundation for future applications in germ cell transplantation and all-female breeding. Full article

Short fruiting branch cotton (SFBC) has a compact plant architecture suitable for dense planting. Plant population density (PPD) and topping are important agronomic practices to achieve high yielding by optimizing cotton plant structure. However, their individual and interactive effects on SFBC growth and yield are poorly understood. This study aimed to explore cotton growth and yield responses to various combinations of PPD and topping time (TT) and the underlying physio-ecological mechanism. Four combinations were included in a two-year field experiment (2023–2024) involving two PPD levels (5.3 plants m⁻², low density LD; 8 plants m⁻², high density HD) and two TT levels (early topping for leaving ten sympodials per plant ET; late topping for leaving fifteen sympodials per plant LT), and compared in terms of biomass accumulation, photosynthetically active radiation capture, and leaf senescence during entire reproductive growth period. Compared to the other three combinations, the combination of HD and LT (HDLT) achieved a higher lint yield due to a greater biological yield, which was predominantly attributed to the higher average rate during the rapid biomass increasing period. Owing to delayed leaf senescence caused by the HD and the LT, the HDLT performed better in leaf senescence-related attributes at the late growth stage. Moreover, these improved attributes also contributed to a higher radiation interception rate and photosynthetic efficiency at the late growth stage. Taken together, combining high density with later topping tends to increase the lint yield of SFBC through increasing dry matter accumulation, delaying leaf senescence, and enhancing canopy radiation interception rate at the late growth. Full article

This study investigated the impact of slow cooling on browning and fruit quality at three maturity stages (early, mid and late). Slow cooling reduced core browning in early/mid-harvest pears, as the browning indexes of early-, middle- and late-harvested ‘Yali’ pears at 60 d were 0.13, 0 and 0.1, respectively, preserving firmness and soluble solids. Transcriptomic analysis revealed that upregulated genes in ‘Yali’ pears facilitated stress adaptation via enhanced catalytic activity and phosphorylation. Mid-harvested pears exhibited activation of phosphorus metabolism and DNA repair mechanisms to maintain cellular homeostasis, whereas the late-harvested counterparts showed significant suppression of photosynthesis-related pathways and pyrimidine metabolism, which collectively accelerated senescence progression. Universal downregulation of hormone-response pathways such as ethylene and auxin revealed systemic stress adaptation decline. Then, the PbRAV transcription factors’ role was also studied. EMSA confirmed that GST-PbRAV2 binds to the PbLAC15 promoter, linking RAV2 to laccase regulation. Overripe pears showed PbRAV2 dysregulation, impairing LAC15 suppression and accelerating browning. Findings provide a theoretical basis for using slow cooling to mitigate browning in pear storage. Full article

To calyx persistence in Korla fragrant pear (Pyrus sinkiangensis) significantly impacts fruit marketability, with persistent calyx causing up to 40% reduction in premium-grade fruit yield. Investigating the hormonal mechanisms underlying calyx abscission and persistent in Korla Fragrant Pear, we performed comprehensive phytohormone profiling using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS; EXIONLC system coupled with SCIEX 6500 QTRAP+). Flowers from first-position (persistent-calyx) and fourth-position (deciduous-calyx) inflorescences were collected at six developmental stages (0–10 days after flowering). Fourteen endogenous hormones—ACC, ME-IAA, IPA, TZR, SA, IAA, ICA, IP, tZ, DHJA, ABA, JA-ile, cZ, and JA—were identified in the calyx during the flowering stage. The calyx abscission rate was significantly higher in the fourth position (79%) compared to the first position (32%). ACC and ABA are closely linked to abscission, with increased ACC at 0 DAF signaling early abscission and ABA accumulation accelerating late abscission at 8 DAF. Auxin exhibited spatiotemporal specificity, peaking in first-order flowers at 4–6 DAF, potentially inhibiting abscission by maintaining cell activity. Cytokinins generally decreased, while jasmonates significantly increased during the fourth-position anthesis stage 8–10 DAF, suggesting a role in stress-related senescence. By systematic analysis of the flowers at the first order (persistent calyx) and the fourth order (deciduous calyx) from 0 to 10 days after anthesis, we found three key stages of hormone regulation: early prediction stage (0–2 DAF), ACC accumulation at the fourth order was significantly higher than that at the first order at 0 days after anthesis, ACC accumulation at the early stage predicted abscission; During the middle maintenance stage (4–6 DAF), the accumulation of cytokinin decreased significantly, while the accumulation of IAA increased significantly in the first position (persistent calyx); Execution Phase (8–10 DAF), ABA reached its peak at 8 DAF, coinciding with the final separation time. JA played an important role in the late stage. Gibberellin was undetected, implying a weak association with calyx abscission. Venn diagram identified N6-(delta 2-Isopentenyl)-adenine (IP) in first-position flowers, which may influence calyx persistence or abscission. These findings elucidate hormone interactions in calyx abscission, offering a theoretical basis for optimizing exogenous hormone application to enhance fruit quality. Full article

This study presents a non-invasive approach to monitoring post-harvest fruit quality by applying CO₂ laser photoacoustic spectroscopy (CO₂LPAS) to study the respiration of “Conference” pears from local and commercially stored (supermarket) sources. Concentrations of ethylene (C₂H₄), ethanol (C₂H₆O), and ammonia (NH₃) were continuously monitored under shelf-life conditions. Our results reveal that ethylene emission peaks earlier in supermarket pears, likely due to post-harvest treatments, while ethanol accumulates over time, indicating fermentation-related deterioration. Significantly, ammonia levels increased during the late stages of senescence, suggesting its potential role as a novel biomarker for fruit degradation. The application of CO₂LPAS enabled highly sensitive, real-time detection of trace gases without damaging the fruit, offering a powerful alternative to traditional monitoring methods. Additionally, artificial intelligence (AI) models, particularly convolutional neural networks (CNNs), were explored to enhance data interpretation, enabling early detection of ripening and spoilage patterns through volatile compound profiling. This study advances our understanding of post-harvest physiological processes and proposes new strategies for improving storage and distribution practices for climacteric fruits. Full article

Ethylene-insensitive 3/ethylene-insensitive 3-like (EIN3/EIL) transcription factors are central regulators of ethylene signaling and stress adaptation in plants. However, their roles in Osmanthus fragrans, a globally cherished ornamental and aromatic plant with significant economic value, remain poorly characterized. Here, we identified nine OfEIL genes across eight chromosomes in the O. fragrans “Liuye Jingui” genome. Conserved motif analysis revealed core domains (Motif1/2/4/7), and promoter cis-elements highlighting hormone-related, stress-related, and growth-related regulatory potential. During late flowering stages, six OfEILs (3/4/5/6/7/9) were significantly upregulated. Under 5-azacytidine (AZA, a DNA demethylation agent), OfEIL2 and OfEIL7 were downregulated, whereas the ETH treatment activated OfEIL3/7/8/9. Strikingly, OfEIL7 exhibited dual regulatory roles, correlating strongly with natural flowering progression, AZA-induced demethylation, and ETH responses. Functional divergence was observed in petal senescence, with OfEIL2–5 and OfEIL7–9 showing stage-specific and tissue-specific expression patterns. These results position OfEIL7 as a key hub integrating epigenetic and hormonal signals to modulate floral longevity and stress adaptation. Our study provides the first genome-wide characterization of the EIL family in O. fragrans, offering critical insights for molecular breeding aimed at enhancing ornamental traits and environmental resilience in this economically significant species. Full article

Senescence impacts plant growth and yields in tetraploid potatoes (Solanum tuberosum L.). Because of their homogenous tetraploid features, it is a major challenge to understand the genetic basis and molecular mechanisms of senescence. Here, we identified a novel central senescence regulator (Nicotinate-nucleotide pyrophosphorylase QPT/StNADC) through map-based cloning. Overexpression of StNADC^Z3 accelerated senescence in the late-senescence variety, with NAD content declining by around 40%. CRISPR/Cas9-induced StNADC mutant cr2–11 exhibited extremely early senescence, and the NAD content was reduced by 87% along with reduced chlorophyll content and photosynthesis. Moreover, the downstream products of the NAD synthesis pathway, such as NaMN, NAD, or niacin, can refresh the cr2–11 mutant to grow normally. Further, the transcriptomics and metabolomics data unveiled that the disrupting of StNADC impairs NAD metabolism, accelerating plant senescence through multiple biological levels. Our results show that StNADC is indispensable for NAD synthesis, and targeting the StNADC-mediated NAD synthesis pathway could be a useful strategy to regulate senescence in potato breeding preprograms. Full article

Herpes simplex virus (HSV)-specific CD8⁺ T cells protect mice from herpes infection and disease. However, the phenotype and function of HSV-specific CD8⁺ T cells that play a key role in the “natural” protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) patients (who have never had clinical herpes disease) remain to be determined. We previously reported that symptomatic (SYMP) patients (who have frequent bouts of recurrent ocular herpes disease) had more undifferentiated and dysfunctional HSV-specific CD8⁺ T cells. In contrast, healthy ASYMP individuals maintained a significantly higher proportion of differentiated polyfunctional CD8⁺ T cells. Here, we report that HSV-specific CD8⁺ T cells from 10 SYMP patients, but not HSV-specific CD8⁺ T cells from 10 ASYMP patients, have phenotypic and functional characteristics of cellular senescence, including: (i) high frequency of senescent (CD57⁺) and exhausted (PD-1⁺) CD8⁺ T cells; (ii) late terminally differentiated (KLRG1⁺), non-proliferating CD8⁺ T cells; (iii) HSV-specific CD8⁺ T cells which decreased in number over time and were not homeostatically maintained, as indicated by a reduction in the number of CD127⁺CD8⁺ T cells; (iv) loss of the co-stimulatory molecule CD28 on HSV-specific CD8⁺ T cells; and (v) decreased production of effector molecules (granzyme B and perforin) by HSV-specific CD8⁺ T cells. Our findings provide insights into the role of senescence in HSV-specific CD8⁺ T cells in susceptibility to recurrent herpes and have implications for T-cell-based immunotherapeutic strategies against recurrent herpes in humans. Full article

The way in which alternate wetting and drying irrigation (AWD), as a water-saving practice promoted in rice (Oryza sativa L.) production systems, could enhance the productivity and water use efficiency (WUE) attracts broad attention. This study selected six mid-season indica rice varieties to investigate the impacts of AWD and conventional irrigation (CI) on grain yield, WUE, grain filling, and root traits. A two-year field experiment demonstrated that grain yields and WUE were significantly increased with varietal improvements. With the improvement of varieties, the maximum grain filling rate and mean grain filling rate for both apical superior and basal inferior spikelets were progressively enhanced during the grain filling stage. Compared to CI, AWD significantly enhanced grain yield and WUE. Flag leaf photosynthetic rate and root characteristics, including root weight, root length, root absorbing surface area, root oxidation activity, and zeatin (Z) + zeatin riboside (ZR) contents in panicles, roots, and root bleeding, were superior under AWD across early, mid, and late grain filling stages. Correlation and path analysis showed that improved grain filling in basal inferior spikelets was attributed to delayed root senescence during the grain filling stage under AWD. These results indicated that AWD would be a better irrigation regime to improve yield and WUE by optimizing grain filling and root growth for modern varieties. Full article