Research on the Surface-State Parameterization of a Refill Friction Stir Spot Welding Joint Made of Aluminum Alloy and Its Connection to the Fracture Mode.

Surface features are crucial for assessing welding quality because they serve as an intuitive depiction of the quality of the joint and have a major influence on welding strength. According to the characteristics of the refill friction stir spot welding (RFSSW) process and an analysis of the surface-state and internal morphology of RFSSW joints, a method of predicting the mechanical properties of RFSSW joints based on surface-state characteristics was proposed. In this paper, a laser-ranging sensor was used to characterize the surface state of RFSSW joints, and parametric characterization methods of the surface-state features of RFSSW joints were proposed. On this basis, a support vector machine was used to predict and analyze the fracture mode of RFSSW joints. The accuracy of the analysis of the test samples reached 95.8%. This paper provides a more efficient and convenient new method for the quality evaluation of RFSSW joints.

Targeted mRNA Nanoparticles Ameliorate Blood-Brain Barrier Disruption Postischemic Stroke by Modulating Microglia Polarization.

The ischemic stroke is a major global health concern, with high mortality and disability rates. Unfortunately, there is a dearth of effective clinical interventions for managing poststroke neuroinflammation and blood-brain barrier (BBB) disruption that are crucial for the brain injury evolving and neurological deficits. By leveraging the pathological progression of an ischemic stroke, we developed an M2 microglia-targeting lipid nanoparticle (termed MLNP) approach that can selectively deliver mRNA encoding phenotype-switching interleukin-10 (mIL-10) to the ischemic brain, creating a beneficial feedback loop that drives microglial polarization toward the protective M2 phenotypes and augments the homing of mIL-10-loaded MLNPs (mIL-10@MLNPs) to ischemic regions. In a transient middle cerebral artery occlusion (MCAO) mouse model of an ischemic stroke, our findings demonstrate that intravenously injected mIL-10@MLNPs induce IL-10 production and enhance the M2 polarization of microglia. The resulting positive loop reinforces the resolution of neuroinflammation, restores the impaired BBB, and prevents neuronal apoptosis after stroke. Using a permanent distal MCAO mouse model of an ischemic stroke, the neuroprotective effects of mIL-10@MLNPs have been further validated by the attenuation of the sensorimotor and cognitive neurological deficits. Furthermore, the developed mRNA-based targeted therapy has great potential to extend the therapeutic time window at least up to 72 h poststroke. This study depicts a simple and versatile LNP platform for selective delivery of mRNA therapeutics to cerebral lesions, showcasing a promising approach for addressing an ischemic stroke and associated brain conditions.

Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis.

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS-2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.

The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses - Potential target to regulate neuroinflammation in acute brain injury.

Activating transcription factor 3 (ATF3) is one of the most important transcription factors that respond to and exert dual effects on inflammatory responses. Recently, the involvement of ATF3 in the neuroinflammatory response to acute brain injury (ABI) has been highlighted. It functions by regulating neuroimmune activation and the production of neuroinflammatory mediators. Notably, recent clinical evidence suggests that ATF3 may serve as a potential ideal biomarker of the long-term prognosis of ABI patients. This mini-review describes the essential inflammation modulatory roles of ATF3 in different disease contexts and summarizes the regulatory mechanisms of ATF3 in the ABI-induced neuroinflammation.

Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury.

Macrophage migration inhibitory factor (MIF) is a multifaced protein that plays important roles in multiple inflammatory conditions. However, the role of MIF in endothelial cell (EC) death under inflammatory condition remains largely unknown. Here we show that MIF actively promotes receptor-interacting protein kinase 1 (RIPK1)-mediated cell death under oxygen-glucose deprivation condition. MIF expression is induced by surgical trauma in peripheral myeloid cells both in perioperative humans and mice. We demonstrate that MIF-loaded myeloid cells induced by peripheral surgery adhere to the brain ECs after distal middle cerebral artery occlusion (dMCAO) and exacerbate the blood-brain barrier (BBB) disruption. Genetic depletion of myeloid-derived MIF in perioperative ischemic stroke (PIS) mice with MCAO following a surgical insult leads to significant reduction in ECs apoptosis and necroptosis and the associated BBB disruption. The adoptive transfer of peripheral blood mononuclear cells (PBMC) from surgical MIFΔLyz2 mice to wild-type (WT) MCAO mice also shows reduced ECs apoptosis and necroptosis compared to the transfer of PBMC from surgical MIFf  l/f  l mice to MCAO recipients. The genetic inhibition of RIPK1 also attenuates BBB disruption and ECs death compared to that of WT mice in PIS. The administration of MIF inhibitor (ISO-1) and RIPK1 inhibitor (Nec-1s) can both reduce the brain EC death and neurological deficits following PIS. We conclude that myeloid-derived MIF promotes ECs apoptosis and necroptosis through RIPK1 kinase-dependent pathway. The above findings may provide insights into the mechanism as how peripheral inflammation promotes the pathology in central nervous system.

Effect of spleen-invigorating, Qi-replenishing and blood-arresting formula on zebrafish models with simvastatin-induced hemorrhage caused by spleen failing to control blood, in terms of theory of Traditional Chinese Medicine.

OBJECTIVE: To investigate the hemostasis effect of spleen-invigorating, Qi-replenishing and blood-arresting formula, on a zebrafish models with simvastatin-induced hemorrhage, and with symptom pattern caused by spleen failing to control blood, in terms of theory of Traditional Chinese Medicine (TCM). METHODS: In the first experiment, 60 AB strain wild type zebrafishes were randomly assigned into two groups: normal group and model group. The model group was treated with 50 µM simvastatin for 24 h. The second experiment: The melanin allele mutated Albino strain zebrafishes were divided into normal, model, A group and B group. The observational parameters were as follows: blood flow, velocity of movement, hemorrhage ratio and improvement ratio of hemorrhage. RESULTS: Hemorrhage ratio: in the first experiment, brain hemorrhage ratio was 75%. In the second experiment, heart hemorrhage ratio was 65%. Blood flow: compared with the normal group, there was a significantly decrease in the model group (P < 0.001). Velocity of movement: in the first experimental, compared with the normal group, there was a significantly decrease in the model group (P < 0.001). Improvement ratio of hemorrhage: agents A had little effect in heart hemorrhage of the zebrafish; agents B could reduce heart hemorrhage ratio of the zebrafish, and increase the improvement ratio of hemorrhage. CONCLUSION: The manifestation of zebrafish model with simvastatin-induced hemorrhage is basically similar to that of the clinical symptom pattern caused by spleen's failure to control blood. The Spleen-invigorating, Qi-replenishing and Blood-arresting Formula can reduce the heart hemorrhage ratio of zebrafish induced by simvastatin, and increase the Improvement ratio of hemorrhage.