Qinghao-Biejia Herb Pair attenuates SLE atherosclerosis by regulating macrophage polarization via ABCA1/G1-mediated cholesterol efflux.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinghao-Biejia herb pair (QB) is the core herb pair of "Jieduquyuziyin prescription" and is one of the commonly used herb pairs for the clinical treatment of systemic lupus erythematosus (SLE). Previous studies have shown that QB reduces the expression of inflammatory cytokines like IL-6 and TNF-α in the serum and kidney of MRL/lpr mice. Additionally, it inhibits the expression of TLR4 and MyD88 in the kidney and aorta and reduces the deposition of renal complement C3 and aortic plaque after treatment. These findings suggest that QB has a preventive and therapeutic effect on lupus rats. AIM OF THE STUDY: This study sought to investigate the mechanisms underlying the anti-SLE combined with atherosclerosis activity of the Qinghao-Biejia herb pair. MATERIALS AND METHODS: Drug targets for QB were identified using the HERB database, while targets associated with SLE and atherosclerosis were retrieved from the GeneCards database. The intersection of these drug and disease targets was then analyzed using a protein-protein interaction (PPI) network with GO and KEGG pathway enrichment analysis. In vivo, apolipoprotein E-deficient (ApoE-/-) mice were induced to develop SLE-AS by intraperitoneal injection of pristane and continued feeding of a high-fat diet. The changes in relevant indexes were observed after 12 weeks of gavage treatment with hydroxychloroquine, QB, Q (Qinghao alone), and B (Biejia alone). Bone marrow-derived macrophages from ApoE-/- mice and Raw 264.7 macrophages were used to explore the mechanisms of QB treatment. RESULTS: The levels of inflammatory cytokines in serum and pathological liver changes in mice were improved to varying degrees in the treatment groups. Additionally, there was a reduction in aortic atheromatous plaque formation and some improvement in cholesterol efflux. Furthermore, QB suppressed the expression of inflammatory cytokines in M1 macrophages, suggesting a role in regulating macrophage polarization. CONCLUSION: QB demonstrates clear efficacy for treating SLE-AS, and its therapeutic mechanism may involve the regulation of macrophage phenotypes by promoting cholesterol efflux.

Self-architectural knowledge distillation for spiking neural networks.

Spiking neural networks (SNNs) have attracted attention due to their biological plausibility and the potential for low-energy applications on neuromorphic hardware. Two mainstream approaches are commonly used to obtain SNNs, i.e., ANN-to-SNN conversion methods, and Directly-trained-SNN methods. However, the former achieve excellent performance at the cost of a large number of time steps (i.e., latency), while the latter exhibit lower latency but suffers from suboptimal performance. To tackle the performance-latency trade-off, we propose Self-Architectural Knowledge Distillation (SAKD), an intuitive and effective method for SNNs leveraging Knowledge Distillation (KD). We adopt a bilevel teacher-student training strategy in SAKD, i.e., level-1 involves directly transferring same-architectural pre-trained ANN weights to SNNs, and level-2 encourages the SNNs to mimic ANN's behavior, considering both final responses and intermediate features aspects. Learning with informative supervision signals fostered by labels and ANNs, our SAKD achieves new state-of-the-art (SOTA) performance with a few time steps on widely-used classification benchmark datasets. On ImageNet-1K, with only 4 time steps, our Spiking-ResNet34 model attains a Top-1 accuracy of 70.04%, outperforming the previous same-architectural SOTA methods. Notably, our SEW-ResNet152 model reaches a Top-1 accuracy of 77.30% on ImageNet-1K, setting a new SOTA benchmark for SNNs. Furthermore, we apply our SAKD to various dense prediction downstream tasks, such as object detection and semantic segmentation, demonstrating strong generalization ability and superior performance. In conclusion, our proposed SAKD framework presents a promising approach for achieving both high performance and low latency in SNNs, potentially paving the way for future advancements in the field.

Jieduquyuziyin prescription alleviates SLE complicated by atherosclerosis via promoting cholesterol efflux and suppressing TLR9/MyD88 activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieduquyuziyin prescription (JP), as a traditional Chinese medicine formula, is extensively applied to treat systemic lupus erythematosus (SLE). Its prescription is based on clinical practice and an evidence-based application of traditional medicines. It is approved by use in Chinese hospitals as a clinical prescription that can be directly used. AIM OF THE STUDY: The study aims to elucidate JP's efficacy on lupus-like disease combined with atherosclerosis and to explore its mechanism. MATERIALS AND METHODS: To conduct in vivo experiments, we established a model of lupus-like disease with atherosclerosis in ApoE-/- mice fed a high-fat diet and injected intraperitoneally with pristane. In addition, oxidized low-density lipoprotein (ox-LDL) and a TLR9 agonist (CpG-ODN2395) were utilized to examine the mechanism of JP on SLE combined with AS in RAW264.7 macrophages in vitro. RESULTS: Results indicated that JP reduced hair loss and levels of the spleen index, maintained stable body weight, alleviated kidney damage in mice, and reduced the expression levels of urinary protein, autoantibodies, and inflammatory factors in serum. Furthermore, JP is effective at alleviating the lupus-like symptoms observed in mice. In mice, JP inhibited aortic plaque deposition, stimulated lipid metabolism, and increased the expression of genes that regulate cholesterol efflux, including ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette subfamily G member 1 (ABCG1), scavenger receptor class B type I (SR-BI), and peroxisome proliferator-activated receptor γ (PPAR-γ). In vivo, JP inhibited the expression of the Toll-like receptor 9 (TLR9)-induced signaling pathway, which links TLR9/MyD88/NF-kB to the expression of subsequent inflammatory factors. Furthermore, JP inhibited the expression of TLR9 and MyD88 in vitro. In addition, the JP treatment effectively reduced foam cell formation in RAW264.7 macrophages by increasing the expression of ABCA1/G1, PPAR-γ and SR-BI. CONCLUSIONS: JP played a therapeutic role in ApoE-/- mice with pristane-induced lupus-like diseases and AS, possibly through inhibition of TLR9/MyD88 signaling and promotion of cholesterol efflux.

Effect of Irrigation and Fertilizer Management on Rice Yield and Nitrogen Loss: A Meta-Analysis.

Irrigation and nitrogen fertilizer application are two important factors affecting yield and nitrogen loss in rice fields; however, the interaction effects of different irrigation schedules and combined management of nitrogen fertilizer application on yield and nitrogen loss in rice fields remain unknown. Therefore, we collected 327 sets of data on rice yield and 437 sets of data on nitrogen loss in rice fields from 2000 to 2021 and investigated the effects of different water-saving irrigation schedules, nitrogen application levels, and water-nitrogen couplings on rice yield, nitrogen use efficiency, and nitrogen loss (N2O emissions, nitrogen runoff, nitrogen leaching, and ammonia volatilization) by meta-analysis using conventional flooding irrigation and no nitrogen treatment as controls. The results showed that alternate wet and dry irrigation and controlled irrigation had increasing effects on rice yield. Alternate wet and dry irrigation had a significant yield-increasing effect (average 2.57% increase) and dry cultivation significantly reduced rice yield with an average 21.25% yield reduction. Water-saving irrigation reduces nitrogen runoff and leaching losses from rice fields but increases N2O emissions, and alternate wet and dry irrigation has a significant effect on increasing N2O emissions, with an average increase of 67.77%. Most water-saving irrigation can increase nitrogen use efficiency. Among water-saving irrigation methods, the effect of controlled irrigation on increasing nitrogen use efficiency is 1.06%. Rice yield and nitrogen use efficiency both showed a trend of increasing then decreasing with nitrogen fertilizer application, and nitrogen loss gradually increased with the amount of nitrogen fertilizer input. Water-nitrogen coupling management can significantly reduce nitrogen loss in rice fields while saving water and increasing yield. Based on the analysis of the data in this study, when the irrigation amount was 300~350 mm and the nitrogen application amount was 200~250 kg/ha, the rice yield and nitrogen fertilizer use efficiency were at a high level, which corresponded to the irrigation schedule of controlled irrigation or alternating wet and dry irrigation in the literature. However, different rice-growing areas are affected by rainfall and land capability, etc. Further optimization and correction of the adapted water and fertilizer management system for paddy fields are needed. The optimal water-nitrogen pattern of this study can achieve high rice yield and reduce nitrogen loss.