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Prion diseases are a group of fatal neurodegenerative disorders characterized by the abnormal folding of cellular prion proteins into pathogenic forms. The development of these diseases is intricately linked to oxidative stress and mitochondrial dysfunction. Irisin, an endogenous myokine, has demonstrated considerable neuroprotective potential due to its antioxidative properties. However, the protective effects of irisin against prion diseases have yet to be clarified. Our findings indicate that treatment with exogenous irisin can mitigate the apoptosis induced by PrP 106–126. Additionally, irisin significantly reduces oxidative stress and alleviates the mitochondrial dysfunction triggered by PrP 106–126 . Furthermore, irisin treatment targets uncoupling protein 2 (UCP2) and activates the AMPK-Nrf2 pathway, substantially improving oxidative stress and mitochondrial dysfunction in N2a cells induced by PrP 106–126 . These results suggest that irisin represents a novel and promising therapeutic approach for treating prion diseases. Highlights PrP 106–126 induces mitochondrial dysfunction in a mtROS-dependent manner. Irisin alleviates PrP 106–126 -induced oxidative stress via UCP2 activation. UCP2 mediates irisin-induced AMPK-Nrf2 activation. Inhibition of oxidative stress rescues PrP 106–126 -induced cell death. PrP 106–126 exposure induces ROS accumulation, leading to mitochondrial dysfunction and cell death. Irisin has a protective effect against PrP 106–126 toxicity and depends on the activation of the UCP2-AMPK signaling pathway.

Proper mitochondrial performance is imperative for the maintenance of normal neuronal function to prevent the development of neurodegenerative diseases. Persistent accumulation of damaged mitochondria plays a role in prion disease pathogenesis, which involves a chain of events that culminate in the generation of reactive oxygen species and neuronal death. Our previous studies have demonstrated that PINK1/Parkin-mediated mitophagy induced by PrP 106−126 is defective and leads to an accumulation of damaged mitochondria after PrP 106−126 treatment. Externalized cardiolipin (CL), a mitochondria-specific phospholipid, has been reported to play a role in mitophagy by directly interacting with LC3II at the outer mitochondrial membrane. The involvement of CL externalization in PrP 106−126 -induced mitophagy and its significance in other physiological processes of N2a cells treated with PrP 106−126 remain unknown. We demonstrate that the PrP 106−126 peptide caused a temporal course of mitophagy in N2a cells, which gradually increased and subsequently decreased. A similar trend in CL externalization to the mitochondrial surface was seen, resulting in a gradual decrease in CL content at the cellular level. Inhibition of CL externalization by knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3 and NDPK-D, responsible for CL translocation to the mitochondrial surface, significantly decreased PrP 106−126 -induced mitophagy in N2a cells. Meanwhile, the inhibition of CL redistribution significantly decreased PINK1 and DRP1 recruitment in PrP 106−126 treatment but had no significant decrease in Parkin recruitment. Furthermore, the inhibition of CL externalization resulted in impaired oxidative phosphorylation and severe oxidative stress, which led to mitochondrial dysfunction. Our results indicate that CL externalization induced by PrP 106−126 on N2a cells plays a positive role in the initiation of mitophagy, leading to the stabilization of mitochondrial function.

Background Species of the genus Eimeria cause coccidiosis in chickens, resulting in a huge burden to the poultry industry worldwide. Eimeria tenella is one of the most prevalent chicken coccidia in China, and E. tenella infection causes hemorrhagic cecitis. Methods Using an established model of coccidiosis in chickens combined with necropsy, imaging of pathological tissue sections, and other techniques, we evaluated the gross and microscopic lesions of cecal tissue within 15 days after inoculation with sporulated oocysts and described the endogenetic developmental process and relationship between E. tenella infection and enteritis development in chickens. Results We observed three generations of merogony and gamogony in E. tenella. We observed gross lesions in the cecum from 84 hpi (hours post inoculation) and microscopic lesions from 60 hpi. The lesions in the cecum mainly exhibited hemorrhagic enteritis. Their severity increased with the onset of the second generation of merogony. The lesions began to alleviate by the end of the endogenous stages of E. tenella. Conclusion We show, for the first time, the complete observation of a series of changes in enteritis caused by 5 × 103 E. tenella oocysts. This study provides reference materials for E. tenella research and pathological diagnosis. This study used necropsy, pathological tissue sections, and other techniques to evaluate the gross and microscopic lesions of cecal tissue in multiple periods within 15 days after incubation of sporulated oocysts. A model of necrotizing enteritis in chicken was developed by sporulated Eimeria tenella oocyst (5 × 103) infection. We observed in detail the process of merogony and sexual development in three generations of E. tenella, as well as the macroscopic lesions and histopathologic changes in the cecum that corresponded to their appearance.

Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates. In a cellular model of prion diseases, we found that both SIRT1 protein levels and deacetylase activity decreased, and SIRT1 overexpression and activation significantly ameliorated mitochondrial morphological damage and dysfunction caused by the neurotoxic peptide PrP106–126. Moreover, we found that mitochondrial biogenesis was impaired, and SIRT1 overexpression and activation alleviated PrP106–126-induced impairment of mitochondrial biogenesis in N2a cells. Further studies in PrP106–126-treated N2a cells revealed that SIRT1 regulates mitochondrial biogenesis through the PGC-1α-TFAM pathway. Finally, we showed that resveratrol resolved PrP106–126-induced mitochondrial dysfunction and cell apoptosis by promoting mitochondrial biogenesis through activation of the SIRT1-dependent PGC-1α/TFAM signaling pathway in N2a cells. Taken together, our findings further describe SIRT1 regulation of mitochondrial biogenesis and improve our understanding of mitochondria-related pathogenesis in prion diseases. Our findings support further investigation of SIRT1 as a potential target for therapeutic intervention of prion diseases.

Failed communication between mitochondria and lysosomes causes dysfunctional mitochondria, which may induce mitochondria-related neurodegenerative diseases. Here, we show that RAB7A, a small GTPase of the Rab family, mediates the crosstalk between these two important organelles to maintain homeostasis in N2a cells treated with PrP 106–126 . Specifically, we demonstrate that mitophagy deficiency in N2a cells caused by PrP 106–126 is associated with dysregulated RAB7A localization in mitochondria. Cells lacking RAB7A display decreased mitochondrial colocalization with lysosomes and significantly increased mitochondrial protein expression, resulting in inhibited mitophagy. In contrast, overexpression of GTP-bound RAB7A directly induces lysosome colocalization with mitochondria. Further study revealed that GTP-bound RAB7A protects mitochondrial homeostasis by supporting autophagosome biogenesis. Moreover, we suggest that depletion of RAB7A leads to gross morphological changes in lysosomes, which prevents autophagosome–lysosome fusion and interferes with the breakdown of autophagic cargo within lysosomes. Overexpression of GTP-bound RAB7A can also alleviate PrP 106–126 -induced morphological damage and dysfunction of mitochondria, reducing neuronal apoptosis. Collectively, our data demonstrate that RAB7A successfully drives mitochondria to the autophagosomal lumen for degradation, suggesting that the communication of proteotoxic stress from mitochondria to lysosomes requires RAB7A, as a signaling molecule, to establish a link between the disturbed mitochondrial network and its remodeling. These findings indicate that small molecules regulating mitophagy have the potential to modulate cellular homeostasis and the clinical course of neurodegenerative diseases. Graphical Abstract Proposed model of mitophagy regulated by RAB7A. (1) Accumulating PrP 106–126 induced mitophagy. (2) RAB7A is recruited to mitochondria. (3) ATG5-12 and ATG9A (5) vesicles are recruited to the autophagosome formation sites in a RAB7A-dependent manner. The ATG5-12 complex recruits and anchors LC3-I to form active LC3-II (4), accelerating mitophagosomal formation. The ATG9A vesicles are thought to be a source of membranes for autophagosome assembly. The recruitment of proteins and lipids induces membrane expansion and subsequent closure to form the mitophagosome. (6) Maintenance of the normal low lysosomal PH depends on active (GTP-bound) RAB7A. (7) RAB7A recruits effector molecules responsible for tight membrane interactions, and directly or indirectly, the subsequent autophagosome merges with the lysosome, and the cargo is completely degraded.

Abstract The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.

As one of the cash crops, cotton is facing the threat of abiotic stress during its growth and development. It has been reported that melatonin is involved in plant defense against salt stress, but whether melatonin can improve cotton salt tolerance and its molecular mechanism remain unclear. We investigated the role of melatonin in cotton salt tolerance by silencing melatonin synthesis gene and exogenous melatonin application in upland cotton. In this study, applicating of melatonin can improve salt tolerance of cotton seedlings. The content of endogenous melatonin was different in cotton varieties with different salt tolerance. The inhibition of melatonin biosynthesis related genes and endogenous melatonin content in cotton resulted in the decrease of antioxidant enzyme activity, Ca 2+ content and salt tolerance of cotton. To explore the protective mechanism of exogenous melatonin against salt stress by RNA-seq analysis. Melatonin played an important role in the resistance of cotton to salt stress, improved the salt tolerance of cotton by regulating antioxidant enzymes, transcription factors, plant hormones, signal molecules and Ca 2+ signal transduction. This study proposed a regulatory network for melatonin to regulate cotton’s response to salt stress, which provided a theoretical basis for improving cotton’s salt tolerance.

The subtilisin-like proteases (SBTs) are a large family of serine peptidases that are unique to plants. Previous studies have shown that SBTs are associated with developmental processes and environmental responses. However, comprehensive identification and systematic analysis of the SBT family have not been conducted in cotton. We used bioinformatics methods to analyze the structural characteristics, phylogenetic relationships, gene structures, expression modes, evolutionary relationships, selection pressures and stress responses of SBT gene family members in upland cotton. In this study, we identified 120 and 112 SBTs in the tetraploid cotton species G. hirsutum and G. barbadense, while 67 and 69 SBTs were identified in the diploid species G. arboreum and G. raimondii, respectively; these SBTs were divided into five distinct subfamilies. We identified the SBT gene GhSBT27A, and explore its function through virus-induced gene silencing and transmission electron microscopy. These results suggested that the GhSBT27A gene was involved in the response to drought stress. These results lay a foundation for further study on the drought stress mechanism of cotton.

Manipulating wave propagation and energy collection plays a core role in modern physics, for which topological insulators hosting robust boundary states offer an ideal platform. However, there exist challenges in integrating multiple topological states like two-dimensional (2D) surface state, one-dimensional (1D) hinge state, and zero-dimensional (0D) corner state into a single three-dimensional (3D) architecture. Here we introduce a dimensional hierarchy acoustic structure with a piled 3D Kagome-chain crystal. By tuning the inter- and intra-layer hopping, we lift the 3D bulk states into 2D surface states. A further distortion on the in-plane unit cell makes the system support the 1D hinge and 0D corner states simultaneously. This hierarchy keeps the parent architecture unchanged. Analytically, we prove the robustness of our framework in different geometrical configurations. Our research offers insight for the practical use of the sonic or optical device with diversified topological modes like wave concentrations and transmissions. The paper presents interesting studies on tunable higher-order topological states of acoustic systems. A 3D structure based on an in-plane Kagome lattice and an out-of-plane Su-Schrieffer-Heeger chain is proposed, that by engineering couplings in different dimensions can simultaneously host 2D surface states, 1D hinge states and 0D corner states.

Many studies have found that damming a river can change downstream hydrology, sediment transport, channel morphology, and fish habitat. However, little is known about river dam effects on downstream riparian wetland dynamics and their quantitative relationship with hydrological alterations. In this study, hydrological time series and wetland distribution data spanning nearly 40 years (1978–2016) before and after the construction of a large dam in 2005 across the Nenjiang River in Northeast China were used to reveal the impact of dam on the downstream discharge regime and wetland degradation. Hydro-statistical and stepwise multiple regression analyses were performed to quantify the relationship of riparian wetland area with a metrics of 33 hydrological indicators. Dam construction caused decline in peak discharge, flood frequency, and magnitude. Moreover, 150 km riparian wetlands along the downstream of the dam was largely reduced. The count and duration of high flow pulses, 1-day maximum, and date of maximum discharge changed significantly after the dam construction. The hydrological changes have made a significant contribution to the 44% reduction in riparian wetlands following the dam construction. Our results indicated that hydrological alterations caused by dam regulation led to the area reduction of downstream riparian wetlands. The findings provide relevant information for developing best dam operation practices to protect and restore downstream wetland ecosystems.