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Background Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammatory effects, but long-term IA injections cause loss of cartilage. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. Methods CD90 + MCS-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90 + MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of the CD90 + MCSs, stimulating CD90@MV secretion. Poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in the CD90@NP (T-CD90@NP). The chondroprotective effect of T-CD90@NP was validated in rabbit and rat OA models. Results The CD90@MV membrane proteins were similar to that of CD90 + MCSs, indicating that CD90@MV bio-activity was similar to the cartilage proliferation-inducing CD90 + MCSs. CD90@NP binding to injured primary cartilage cells was significantly stronger than to erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, the long-term IA treatment with T-CD90@NP showed significantly enhanced repair of damaged cartilage compared to TA and CD90 + MCS treatments. In the rat OA model, the short-term IA treatment with T-CD90@NP showed effective anti-inflammatory ability similar to that of TA treatment. Moreover, the long-term IA treatment with T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promoted the regeneration of chondrocytes, reduced apoptosis via the FOXO pathway, and influenced type 2 macrophage polarization to regulate inflammation through IL-10. Conclusion This study confirmed that T-CD90@NP promoted chondrocyte proliferation and anti-inflammation, improving the effects of a clinical glucocorticoid treatment plan. Graphical Abstract Highlights Long-term injection of glucocorticoids in the knee joint cavity promotes loss of cartilage content. CD90-positive stem cell vesicles encapsulated with Triamcinolone acetonide-loaded nanoparticles have good materials. T-CD90@NPs drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis. T-CD90@NPs regulate the polarization of type 2 macrophages to resist inflammation. T-CD90@NPs promote chondrocyte regeneration through the FOXO signaling pathway.

Cells utilize calcium ions (Ca 2+ ) to signal almost all aspects of cellular life, ranging from cell proliferation to cell death, in a spatially and temporally regulated manner. A key aspect of this regulation is the compartmentalization of Ca 2+ in various cytoplasmic organelles that act as intracellular Ca 2+ stores. Whereas Ca 2+ release from the large-volume Ca 2+ stores, such as the endoplasmic reticulum (ER) and Golgi apparatus, are preferred for signal transduction, Ca 2+ release from the small-volume individual vesicular stores that are dispersed throughout the cell, such as lysosomes, may be more useful in local regulation, such as membrane fusion and individualized vesicular movements. Conceivably, these two types of Ca 2+ stores may be established, maintained or refilled via distinct mechanisms. ER stores are refilled through sustained Ca 2+ influx at ER-plasma membrane (PM) membrane contact sites (MCSs). In this review, we discuss the release and refilling mechanisms of intracellular small vesicular Ca 2+ stores, with a special focus on lysosomes. Recent imaging studies of Ca 2+ release and organelle MCSs suggest that Ca 2+ exchange may occur between two types of stores, such that the small stores acquire Ca 2+ from the large stores via ER-vesicle MCSs. Hence vesicular stores like lysosomes may be viewed as secondary Ca 2+ stores in the cell.

Organelles are tiny structures with specific functions in eukaryotic cells. Since they are covered with membranes, different organelles can perform biological processes that are incompatible. Organelles can also actively communicate with each other to maintain cellular homeostasis the vesicular trafficking pathways and membrane contact sites (MCSs), which allow the exchange of metabolites and other information required for normal cellular physiology. An imbalance in organelle interactions may result in multiple pathological processes. Growing evidence shows that abnormal organelle communication contributes to cellular senescence and is associated with organ aging. However, the key role of organelle interactions in aging has not yet been broadly reviewed and fully investigated. In this review, we summarize the role of organelle interactions in cellular senescence, and highlight their relevance for cellular calcium homeostasis, protein and lipid homeostasis, and mitochondrial quality control. Our review reveals important mechanisms of organelle interactions in cellular senescence and provides important clues for intervention strategies from a new perspective.

The endoplasmic reticulum (ER) forms direct membrane contact sites with the plasma membrane (PM) in eukaryotic cells. These ER-PM contact sites play essential roles in lipid homeostasis, ion dynamics, and cell signaling, which are carried out by protein-protein or protein-lipid interactions. Distinct tethering factors dynamically control the architecture of ER-PM junctions in response to intracellular signals or external stimuli. The physiological roles of ER-PM contact sites are dependent on a variety of regulators that individually or cooperatively perform functions in diverse cellular processes. This review focuses on proteins functioning at ER-PM contact sites and highlights the recent progress in their mechanisms and physiological roles.

Tropical cyclogenesis (TCG) remains an elusive phenomenon partly due to the limited understanding of complex water vapor‐convection‐wave interactions. The Model for Prediction Across Scales‐Atmosphere (MPAS‐A) was used to study the TCG of the African easterly wave (AEW) that became Hurricane Helene (2006). The two main objectives were: (a) evaluate the capability of MPAS‐A to simulate TCG from an AEW by comparing MPAS‐A—initialized with the Integrated Forecasting System (IFS) and the Global Forecast System (GFS)—with observations together with reanalysis and, (b) use the hindcast to investigate the role of moisture in the mechanisms that led to Helene's TCG. The more intense GFS‐initialized pre‐Helene was slower propagating and was associated with a wetter and stronger monsoon when compared to both the IFS‐initialized simulation and observed. TCG occurred when net moisture flux within the boundary layer toward the center of the wave increased persistently. The reanalysis pre‐genesis top‐heavy vertical mass flux profile transitioned to a bottom‐heavy profile during TCG, whereas the simulations had top‐heavy and bottom‐heavy profiles simultaneously, resulting from a more‐intense and fast‐occurring TCG than in the reanalysis. Moisture‐vortex instability helped explain the vertical mass fluxes and the co‐location of convection, moisture and wave vortex demonstrating to be an applicable theoretical model for TCG. Moisture mode was tested as a diagnostic tool for AEW evolution and TCG. The case exhibited some moisture mode properties, and it is proposed that AEWs become more moisture‐mode like once reaching western Africa and during TCG. An AEW TCG pathway is proposed. Plain Language Summary The formation of a tropical cyclone (TC) is a complex process that is difficult to predict, mainly because we are still trying to understand the roles of water vapor and cloud systems in this process. Weather and climate models are used to better understand how water vapor and cloud systems interact with TC seedlings like African easterly waves (AEWs). In this study, one of those models was used to go back in time and perform a detailed study of one of those waves that became a TC. This study revealed that the model was capable of simulating the evolution of the AEW into a TC. It was also demonstrated that continuous moisture input toward the center of the TC‐seedling circulation close to the surface was essential for the genesis of the TC. Cloud systems that grew (thanks to that moisture surplus) and moved with the TC seedling center were major contributors to the genesis of this TC. Because the genesis was shown to be driven by moisture‐cloud system feedbacks during TC genesis, this wave was categorized as a type of mixed‐off‐equatorial moisture mode. Key Points The Model for Prediction Across Scales is capable of reproducing the evolution and growth of pre‐Helene from an African easterly wave Boundary‐layer moisture flux was key in Helene's moisture‐driven tropical cyclogenesis (TCG) Helene’s TCG had convection and moisture co‐located with the wave vortex, indicative of moisture‐vortex instability

Humic acids (HAs) are widely used as adsorbents or carriers, yet they still lack oxygenic functional groups under certain conditions. Modification via catalytic oxidation under mild conditions is an ideal method to increase the oxygenic functional groups in HAs—if simple catalyst separation could be realized. Here, we report the use of CuO nanoparticles supported by Fe3O4 magnetic nanospheres as magnetic catalytic systems (MCSs) that could catalyze HA modification via Fenton oxidation. These MCSs can be easily magnetically separated from the products. The content of carboxyl groups increased from 2.45% to 10.47% after reaction, while the yield of modified HAs remained approximately 100%. These results indicate that oxidation with MCSs could be a potential method for HA modification.

Organelles, despite having distinct functions, interact with each other. Interactions between organelles typically occur at membrane contact sites (MCSs) to maintain cellular homeostasis, allowing the exchange of metabolites and other pieces of information required for normal cellular physiology. Imbalances in organelle interactions may lead to various pathological processes. Increasing evidence suggests that abnormalorganelle interactions contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the key role of organelle interactions in NAFLD has not been fully evaluated and researched. In this review, we summarize the role of organelle interactions in NAFLD and emphasize their correlation with cellular calcium homeostasis, lipid transport, and mitochondrial dynamics.

Since 2020, southern Brazil’s Rio Grande do Sul (RS) State has been affected by extreme precipitation episodes caused by different atmospheric systems. However, the most extreme was registered between the end of April and the beginning of May 2024. This extreme precipitation caused floods in most parts of the state, affecting 2,398,255 people and leading to 183 deaths and 27 missing persons. Due to the severity of this episode, we need to understand its drivers. In this context, the main objective of this study is a multi-scale analysis of the extreme precipitation between 26 April and 5 May, i.e., an analysis of the large-scale patterns of the atmosphere, a description of the synoptic environment, and an analysis of the mesoscale viewpoint (cloud-top features and lightning). Data from different sources (reanalysis, satellite, radar, and pluviometers) were used in this study, and different methods were applied. The National Center for Monitoring and Early Warning of Natural Disasters (CEMADEN) registered accumulated rainfall above 400 mm between 26 April and 5 May using 27 pluviometers located in the central-northern part of RS. The monthly volumes reached 667 mm and 803 mm, respectively, for April and May 2024, against a climatological average of 151 mm and 137 mm for these months. The maximum precipitation recorded was 300 mm in a single day on 30 April 2024. From a large-scale point of view, an anomalous heat source in the western Indian Ocean triggered a Rossby wave that contributed to a barotropic anticyclonic anomalous circulation over mid-southeastern Brazil. While the precipitant systems were inhibited over this region (the synoptic view), the anomalous stronger subtropical jet southward of the anticyclonic circulation caused uplift over RS State and, consequently, conditions leading to mesoscale convective system (MCS) development. In addition, the low-level jet east of the Andes transported warm and moist air to southern Brazil, which also interacted with two cold fronts that reached RS during the 10-day period, helping to establish the precipitation. Severe deep MCSs (with a cloud-top temperature lower than −80 °C) were responsible for a high lightning rate (above 10 flashes km−2 in 10 days) and accumulated precipitation (above 600 mm in 10 days), as observed by satellite measurements. This high volume of rainfall caused an increase in soil moisture, which exceeded a volume fraction of 0.55, making water infiltration into the soil difficult and, consequently, favoring flood occurrence.

With the emergence of new technologies, mobile devices are capable of undertaking computational and sensing tasks. A large number of users with these mobile devices promote the formation of the Mobile Crowdsourcing Systems (MCSs). Within a MCS, each mobile device can contribute to the crowdsourcing platform and get rewards from it. In order to achieve better performance, it is important to design a mechanism that can attract enough participants with mobile devices and then allocate the tasks among participants efficiently. In this paper, we are interested in the investigation of tasks allocation and price determination in MCSs. Two truthful auction mechanisms are proposed for different working patterns. A Vickrey–Clarke–Groves (VCG)-based auction mechanism is proposed to the continuous working pattern, and a suboptimal auction mechanism is introduced for the discontinuous working pattern. Further analysis shows that the proposed mechanisms have the properties of individual rationality and computational efficiencies. Experimental results suggest that both mechanisms guarantee all the mobile users bidding with their truthful values and the optimal maximal social cost can be achieved in the VCG-based auction mechanism.

Mitochondrial network is constantly in a dynamic and regulated balance of fusion and fission processes, which is known as mitochondrial dynamics. Mitochondria make physical contacts with almost every other membrane in the cell thus impacting cellular functions. Mutations in mitochondrial dynamics genes are known to cause neurogenetic diseases. To better understand the consequences on the cellular phenotype and pathophysiology of neurogenetic diseases associated with defective mitochondrial dynamics, we have compared the fibroblasts phenotypes of (i) patients carrying pathogenic variants in genes involved in mitochondrial dynamics such as DRP1 (also known as DNM1L), GDAP1, OPA1 and MFN2, and (ii) patients carrying mutated genes that their dysfunction affects mitochondria or induces a mitochondrial phenotype, but that are not directly involved in mitochondrial dynamic network, such as FXN (encoding frataxin, located in the mitochondrial matrix), MED13 (hyperfision phenotype) and CHKB (enlarged mitochondria phenotype). We identified mitochondrial network alterations in all patients’ fibroblasts except for CHKBQ198*/Q198*. Functionally, all fibroblasts showed mitochondrial oxidative stress, without membrane potential abnormalities. The lysosomal area and distribution were abnormal in GDAP1W67L/W67L, DRP1K75E/+, OPA1F570L/+ and FXNR165C/GAA fibroblasts. These lysosomal alterations correlated with mitochondria-lysosome membrane contact sites (MCSs) defects in GDAP1W67L/W67L exclusively. The study of mitochondrial contacts in all samples further revealed a significant decrease in MFN2R104W/+ fibroblasts. GDAP1 and MFN2 are outer mitochondrial membrane (OMM) proteins and both are related to Charcot-Marie Tooth neuropathy. Here we identified their constitutive interaction as well as MFN2 interaction with LAMP-1. Therefore MFN2 is a new mitochondria-lysosome MCSs protein. Interestingly, GDAP1W67L/W67L and MFN2R104W/+ fibroblasts carry pathogenic changes that occur in their catalytic domains thus suggesting a functional role of GDAP1 and MFN2 in mitochondria–lysosome MCSs. Finally, we observed starvation-induced autophagy alterations in DRP1K75E/+, GDAP1W67L/W67L, OPA1F570L/+, MFN2R104W/+ and CHKBQ198*/Q198* fibroblasts. These genes are related to mitochondrial membrane structure or lipid composition, which would associate the OMM with starvation-induced autophagy. In conclusion, the study of mitochondrial dynamics and mitochondria-lysosome axis in a group of patients with different neurogenetic diseases has deciphered common and unique cellular phenotypes of degrading and non-degrading pathways that shed light on pathophysiological events, new biomarkers and pharmacological targets for these disorders.