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Beta cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In recent years, the role played by beta cells in the development of T1D has evolved from passive victims of the immune system to active contributors in their own destruction. We and others have demonstrated that perturbations in the islet microenvironment promote endoplasmic reticulum (ER) stress in beta cells, leading to enhanced immunogenicity. Among the underlying mechanisms, secretion of extracellular vesicles (EVs) by beta cells has been suggested to mediate the crosstalk with the immune cell compartment. To study the role of cellular stress in the early events of T1D development, we generated a novel cellular model for constitutive ER stress by modulating the expression of , which encodes BiP/GRP78, in EndoC-βH1 cells. To investigate the role of EVs in the interaction between beta cells and the immune system, we characterized the EV miRNA cargo and evaluated their effect on innate immune cells. Analysis of the transcriptome showed that knockdown resulted in the upregulation of signaling pathways involved in the unfolded protein response (UPR) and changes the miRNA content of EVs, including reduced levels of miRNAs involved in IL-1β signaling. Treatment of primary human monocytes with EVs from stressed beta cells resulted in increased surface expression of CD11b, HLA-DR, CD40 and CD86 and upregulation of IL-1β and IL-6. These findings indicate that the content of EVs derived from stressed beta cells can be a mediator of islet inflammation.

Type 1 diabetes (T1D) is a chronic autoimmune disorder characterised by an autoimmune response specifically mounted against the insulin-producing beta cells. Within the islet, high cellular connectivity and extensive vascularisation facilitate intra-islet communication and direct crosstalk with the surrounding tissues and the immune system. During the development of T1D, cytokines and extracellular vesicles released by beta cells can contribute to the recruitment of immune cells, further amplifying autoimmunity and aggravating beta cell damage and dysfunction. In this review, we will evaluate the role of beta-cell-derived extracellular vesicles as mediators of the autoimmune response and discuss their potential for early diagnosis and new therapeutic strategies in T1D.

Background Giardia duodenalis is an extracellular protozoan parasite that causes giardiasis in mammals. The presentation of giardiasis ranges from asymptomatic to severe diarrhea, and the World Health Organization lists it in the Neglected Diseases Initiative. Extracellular vesicles (EVs) are a key mediator of intracellular communication. Although previous studies have shown that G. intestinalis can regulate a host’s innate immune response, the role of G. intestinalis EVs (GEVs) in triggering a G. intestinalis- induced innate immune response remains to be further explored. Methods In this study, GEVs, G. intestinalis and GEVs + G. intestinalis were inoculated into macrophages, respectively. The transcription and secretion levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α), were measured using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs). The phosphorylation levels of the MAPK, AKT and NF-κB signaling pathways in GEV-stimulated mouse macrophages were examined using western blotting and immunofluorescence methods. The roles of activated pathways in the GEV-triggered inflammatory response were determined using inhibition assays, western blotting and ELISAs. Results The results showed that pretreatment with GEVs enhanced with G. intestinalis (GEVs + G. intestinalis ) induced IL-1β, IL-6 and TNF-α transcription and secretion from mouse macrophages compared to stimulation with either GEVs or G. intestinalis alone. Inoculation of mouse macrophages with GEVs upregulated the phosphorylation levels of the p38 MAPK, p44/42 MAPK (Erk1/2), AKT and NF-κB signaling pathways and led to the nuclear translocation of NF-κB p65. Blocking the activated p38, Erk and NF-κB signaling pathways significantly downregulated the secretion of proinflammatory cytokines, and blocking the activated AKT signaling pathway demonstrated reverse effects. Conclusions The results of this study reveal that GEVs can enhance G. intestinalis- induced inflammatory response levels in mouse macrophages through activation of the p38, ERK and NF-κB signaling pathways. The role of GEVs in regulating host cell immune responses may provide insights into exploring the underlying mechanisms in G. intestinalis –host interactions. Graphical abstract

Giardia duodenalis , also known as Giardia lamblia or Giardia intestinalis , is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of G. duodenalis ; however, whether TLR9 has a role in innate immune responses against Giardia infection remains unknown. In the present study, various methods, including reverse transcriptase–quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against G. lamblia virus (GLV)–free or GLV-containing Giardia trophozoites. The results revealed that in G. duodenalis– stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, G. duodenalis stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the G. duodenalis –induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that G. duodenalis may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our in vitro findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of G. duodenalis .

This study aims to explore the association between hematoma expansion, edema development, and patient prognosis in hemorrhagic stroke patients. Utilizing clinical information, imaging characteristics, and prognostic data from 160 hemorrhagic stroke patients, several predictive models were constructed to examine the pathological progression and outcomes of these patients. Specifically, data preprocessing was employed to calculate the time intervals between each examination and select data within 48 hours for analyzing changes in hematoma volume and its percentage. This facilitated the determination of hematoma expansion within the first 48 hours post-onset, with results documented in a dedicated table. Employing the XGBoost model, both the test and training datasets were trained to develop a predictive model for hematoma expansion. Upon evaluation, the model demonstrated a 75% accuracy rate in predicting hematoma expansion across all patients (sub001-sub160). This study underscores the potential of using advanced predictive modeling, such as XGBoost, to enhance the prognosis assessment and clinical decision-making in hemorrhagic stroke care.

Giardia duodenalis is an extracellular protozoan parasite that causes giardiasis in mammals. The presentation of giardiasis ranges from asymptomatic to severe diarrhea, and the World Health Organization lists it in the Neglected Diseases Initiative. Extracellular vesicles (EVs) are a key mediator of intracellular communication. Although previous studies have shown that G. intestinalis can regulate a host's innate immune response, the role of G. intestinalis EVs (GEVs) in triggering a G. intestinalis-induced innate immune response remains to be further explored. In this study, GEVs, G. intestinalis and GEVs + G. intestinalis were inoculated into macrophages, respectively. The transcription and secretion levels of proinflammatory cytokines, including interleukin (IL)-1[beta], IL-6 and tumor necrosis factor alpha (TNF-[alpha]), were measured using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs). The phosphorylation levels of the MAPK, AKT and NF-κB signaling pathways in GEV-stimulated mouse macrophages were examined using western blotting and immunofluorescence methods. The roles of activated pathways in the GEV-triggered inflammatory response were determined using inhibition assays, western blotting and ELISAs. The results showed that pretreatment with GEVs enhanced with G. intestinalis (GEVs + G. intestinalis) induced IL-1[beta], IL-6 and TNF-[alpha] transcription and secretion from mouse macrophages compared to stimulation with either GEVs or G. intestinalis alone. Inoculation of mouse macrophages with GEVs upregulated the phosphorylation levels of the p38 MAPK, p44/42 MAPK (Erk1/2), AKT and NF-κB signaling pathways and led to the nuclear translocation of NF-κB p65. Blocking the activated p38, Erk and NF-κB signaling pathways significantly downregulated the secretion of proinflammatory cytokines, and blocking the activated AKT signaling pathway demonstrated reverse effects. The results of this study reveal that GEVs can enhance G. intestinalis-induced inflammatory response levels in mouse macrophages through activation of the p38, ERK and NF-κB signaling pathways. The role of GEVs in regulating host cell immune responses may provide insights into exploring the underlying mechanisms in G. intestinalis-host interactions.

TiAIN solar selective absorbing coatings which were deposited on 304L stainless steel using cathodic arc evaporation method were annealed under non-vacuum at different temperatures with different times. The optical properties （absorptance and emittance） of the coatings were measured by a spectrophotometer. It was found that, after being annealed for 2 hours at different temperatures, the absorptance of the coatings reached the highest value of 0.92 at 700 ℃ while the emittance got the lowest value of 0.38 at 800 ℃. When the coatings were annealed at 600 ℃ for 24 hours, the optical properties changed to 0.92/0.44 （absorptance/ emittance）. By measuring the structure, morphology, elements and surface roughness of the coatings, it was found that both the elemental composition and the surface roughness of the coatings changed as a result of annealing, and these changes caused the change of the optical properties of the coatings.

Although effective and practical YOLO methods have dominated the field of object detection, they rely on predefined and trained object categories, which limits their broad application. To overcome this limitation, YOLO-World enhances YOLO’s open-vocabulary detection capabilities through modeling visual language and pretraining on large-scale datasets. Therefore, this manuscript proposes an improved object detection and segmentation model based on YOLO-World-S to improve detection efficiency and accuracy. The computational complexity and memory usage are reduced by introducing large-kernel separable convolutions into the RepVL-PAN of YOLO-World-S. The Neck incorporates a dynamic sparse attention mechanism (PSBRA module) to reduce the computational cost of traditional multi-head self-attention, while facilitating the integration of YOLO-World-S with EfficientSAM. In addition, the loss function is reconstructed to effectively resolve conflicts on shared features or optimization objectives between object detection and segmentation tasks. This method achieves mAPs (mean average precisions) of 58.8% and 308 FPSs (frames per second) on the COCO dataset, improving both accuracy and speed compared with those of the original baseline model.

[This corrects the article DOI: 10.1371/journal.pone.0315512.].

The Earth’s diffuse auroral precipitation provides the major source of energy input into the nightside upper atmosphere and acts as an essential linkage of the magnetosphere-ionosphere coupling. Resonant wave-particle interactions play a dominant role in the scattering of injected plasma sheet electrons, leading to the diffuse auroral precipitation. We review the recent advances in understanding the origin of the diffuse aurora and in quantifying the exact roles of various magnetospheric waves in producing the global distribution of diffuse auroral precipitation and its variability with the geomagnetic activity. Combined scattering by upper-and lower-band chorus accounts for the most intense inner magnetospheric electron diffuse auroral precipitation on the nightside. Dayside chorus can be responsible for the weaker dayside electron diffuse auroral precipitation. Pulsating auroras, the dynamic auroral structures embedded in the diffuse aurora, can be mainly caused by modulation of the excitation of lower band chorus due to macroscopic density variations in the magnetosphere. Electrostatic electron cyclotron harmonic waves are an important or even dominant cause for the nightside electron diffuse auroral precipitation beyond ∼ 8 R e and can also contribute to the occurrence of the pulsating aurora at high L -shells. Scattering by electromagnetic ion cyclotron waves could quite possibly be the leading candidate responsible for the ion precipitation (especially the reversed-type events of the energy-latitude dispersion) in the regions of the central plasma sheet and ring current. We conclude the review with a summary of current understanding, outstanding questions, and a number of suggestions for future research.