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Astrocyte‐microglia crosstalk is vital for neuronal survival and clearing aggregate accumulation in neurodegenerative diseases. While interleukin‐3 (IL‐3) has been reported to exert both protective and detrimental effects in neurodegenerative diseases, however, its role in α‐synuclein pathology remains unclear. In this study, it is found that astrocytic IL‐3 and microglial IL‐3R are positively responsive to α‐synuclein pathology in the brains of transgenic A53T Parkinson's disease (PD) mice and in an adeno‐associated virus (AAV)‐human α‐synuclein (AAV‐hα‐Syn)‐injected PD mouse model. Exogenous IL‐3 infusion reduces behavioral abnormities and nigrostriatal α‐synuclein pathology. Mechanistically, IL‐3 induces microglial phagocytosis of pathological α‐synuclein while simultaneously stimulating dopaminergic (DA) neurons to clear pathological α‐synuclein via induction of autophagy through the IFN‐β/Irgm1 pathway. Due to its limited efficiency in crossing the blood–brain barrier, a precise IL‐3 delivery strategy is developed by cross‐linking IL‐3 and RVG29 with PEG‐Linker (RVG‐modified IL‐3 nanogels—RVG‐IL3 NGs). Intravenous administration of RVG‐IL3 NGs shows efficient uptake by microglia and DA neurons within the brain. RVG‐IL3 NGs ameliorate motor deficits and pathological α‐synuclein by improving microglial and neuronal function in the AAV‐hα‐Syn mouse model of PD. Collectively, IL‐3 may represent a feasible therapeutic strategy for PD. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) causes abortions, stillbirths, and dummy pregnancies. Previous studies found that PRRSV can promote secondary bacterial infections and elevate bacterial endotoxin levels, further increasing the abortion rate in sows. However, the pathways by which bacterial endotoxins invade the bodies of PRRSV(+) sows and aggravate their clinical symptoms are unknown. In this study, we established a model of PRRSV and lipopolysaccharide (LPS) working together on porcine endometrial epithelial cells (PEECs). We speculate that PRRSV and LPS affect PEECs through viral protein interaction with cytokines and cytokine receptors, natural killer cell-mediated cytotoxicity, and regulation of actin cytoskeleton signaling pathways by analyzing seq-RNA. The PRRSV proteins act on inflammatory factors and their receptors to activate chemokines-5 (CCL5), chemokines-4 (CCL4), and chemokines-8 (CCL8) mRNA expression, causing severe inflammatory reactions. In addition, the elevation of MEK1/2 factors and the integrins acting on NK cells promote the upregulation of VAV1/Tiam1, RAC, and IRSp53, leading to increased expression of Arp2/3 and F-actin in PEECs in the PRRSV + LPS(+) groups. However, the highly expressed cell microfilaments and cytoskeleton disrupt the original network structure, causing changes in the original physiological function of the PEECs. In summary, the PRRSV protein interacts with cytokines and cytokine receptors of PEECs, thereby enhancing virus-mediated chemokine factors and their receptor activity, accelerating bacterial endotoxin entry into the body and the invasion of cells. They destroy the cytoskeletal structure of the cells and increase damage to uterine tissue. [ABSTRACT FROM AUTHOR]

Double-site catalysts have attracted widespread attention in the field of electrocatalysis due to their high metal loading, adjustable active centres, and electronic valence states. However, the development of bimetallic sites catalysts that coordinate with definite atoms is still in the exploratory stage. Here, we designed and synthesized a bimetallic palladium complex (BPB-Pd2) with conjugated backbone. The supported BPB-Pd2 was applied to electrochemical CO2 reduction reaction (CO2RR) for the first time. The as-obtained BPB-Pd2 gives an exceptional Faradaic efficiency of CO (FECO) of 94.4% at −0.80 V vs. reversible hydrogen electrode (RHE), which is significantly superior to monoatomic palladium catalyst (BPB-Pd1). The density functional theory (DFT) calculations revealed that the essential reason for the outstanding activity of BPB-Pd2 toward CO2RR was that the electronic effect between diatomic palladium reduces the free energy change for CO2RR process. Thus, BPB-Pd2 exhibits moderate free energy change to form COOH* intermediate, which was beneficial for the generation of CO in CO2RR. [ABSTRACT FROM AUTHOR]