Downregulation of protease activated receptor expression and cytokine production in P815 cells by RNA interference

Abstract Background Protease-activated receptors (PAR) are seven transmembrane G-coupled receptors comprising four genes (PAR-1 ~ PAR-4). Mast cell has been identified to be able to express PARs and release an array of cytokines upon activation. Recently, it was reported that interleukin (IL)-12 could regulate the expression of PARs in mast cells, and tryptase could induce IL-4 and IL-6 release from mast cells. In order to further investigate the issues, RNA interference (RNAi) technique was employed and small interfering RNAs (siRNA) of PARs were transfected in P815 cells. Results The results showed that siRNAs for PAR-1, PAR-2 and PAR-4 significantly downregulated expression of PAR-1, PAR-2 and PAR-4 mRNAs and proteins in P815 cells at 24, 48 and 72 h following transfection. siRNA PAR-1.2 and siRNA PAR-4.2 significantly reduced IL-12 induced upregulation of PAR-1 and PAR-4 expression, respectively when P815 cells were transfected with them for 48 h. siRNA PAR-2.3 blocked IL-12 induced downregulation of PAR-2 expression on both mRNA and protein levels. It was also observed that siRNA PAR-2.3 and siRNA PAR-1.2 reduced trypsin induced IL-4 release by approximately 92.6% and 65.3%, and SLIGKV-NH2 induced IL-4 release by 82.1% and 60.1%, respectively. Similarly, siRNA PAR-2.3 eliminated tryptase-induced IL-4 release by 75.3%, and siRNA PAR-1.2 diminished SFLLR-NH2 induced IL-4 release by 79.3%. However, siRNA PAR-1.2, siRNA PAR-2.3 and siRNA PAR-4.3 at 10 nM did not show any effect on tryptase-induced IL-6 release from P815 cells. Conclusion In conclusion, siRNAs of PARs can modulate PAR expression and PAR related cytokine production in mast cells, confirming that PARs are likely to play a role in allergic reactions.</p

FedPerfix: Towards Partial Model Personalization of Vision Transformers in Federated Learning

Personalized Federated Learning (PFL) represents a promising solution for decentralized learning in heterogeneous data environments. Partial model personalization has been proposed to improve the efficiency of PFL by selectively updating local model parameters instead of aggregating all of them. However, previous work on partial model personalization has mainly focused on Convolutional Neural Networks (CNNs), leaving a gap in understanding how it can be applied to other popular models such as Vision Transformers (ViTs). In this work, we investigate where and how to partially personalize a ViT model. Specifically, we empirically evaluate the sensitivity to data distribution of each type of layer. Based on the insights that the self-attention layer and the classification head are the most sensitive parts of a ViT, we propose a novel approach called FedPerfix, which leverages plugins to transfer information from the aggregated model to the local client as a personalization. Finally, we evaluate the proposed approach on CIFAR-100, OrganAMNIST, and Office-Home datasets and demonstrate its effectiveness in improving the model's performance compared to several advanced PFL methods.Comment: 2023 IEEE/CVF International Conference on Computer Vision (ICCV

Oś MIF/CD74 jako cel terapii metforminą w podocytopatii cukrzycowej — rzeczywista praktyka kliniczna

Introduction：To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms. Methods: 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in combination with metformin (n=102) were enrolled in the study. The amount of macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were determined. Results: Metabolic parameters including fasting blood glucose, postprandial 2 hours blood glucose, hemoglobin A1c, MIF and CD74 in serum were comparable between the two groups. Moreover, metformin add-on therapy showed significantly better efficacy in reducing UMCR, UCCR, UPCR and UACR in comparison with those in sulfonylurea monotherapy group, respectively. UPCR had positive correlation with UACR, UMCR and UCCR (r＝0.73, r=0.69, r=0.62, P < 0.01), respectively. Conclusions: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response. Wstęp: Celem pracy było zaobserwowanie efektów działania metforminy na wydalanie MIF, CD74 i podokaliksyny w moczu pacjentów z cukrzycą typu 2 oraz zbadanie jej możliwych mechanizmów nefroprotekcyjnych. Materiał i metody: W badaniu wzięło udział 202 pacjentów z niewyrównaną cukrzycą typu 2, którym zalecono wcześniej monoterapię sulfonylomocznikiem (n = 100) lub sulfonylomocznikiem skojarzonym z metforminą (n = 102). Podczas badania określono ilość czynnika hamującego migrację makrofagów (MIF) i CD74 w surowicy krwi, wskaźnik MIF/kreatynina (urinary MIF to creatinine ratio; UMCR), wskaźnik CD74/kreatynina (urinary CD74 to creatinine ratio; UCCR), wskaźnik albumina/kreatynina (urinary albumin to creatinine ratio; UACR) oraz wskaźnik podokaliksyna/kreatynina (urinary podocalyxin to creatinine ratio; UPCR). Wyniki: Parametry metaboliczne, w tym glikemia na czczo, stężenie glukozy we krwi dwie godziny po posiłku, hemoglobina A1c, MIF i CD74 w surowicy krwi były porównywalne w obu grupach. Ponadto, terapia z dodatkiem metforminy wykazała znacznie lepszą skuteczność w redukowaniu wskaźników UMCR, UCCR, UPCR i UACR w porównaniu z grupą, w której zastosowano monoterapię sulfonylomocznikiem. Wskaźnik UPRC wykazywał dodatnią korelację ze wskaźnikami UACR, UMCR i UCCR (odpowiednio: r = 0,73, r = 0,69, r = 0,62, p &lt; 0,01). Wnioski: Metformina może wykazywać zdolność do ochrony podocytów u pacjentów z cukrzycą typu 2, a mechanizmy leżące u pod­staw tego procesu mogą być częściowo przypisane jej właściwościom hamowania kaskady reakcji zapalnych zależnych od osi MIF-CD74

Synthesis of MoS2 nanoparticles using MoO3 nanobelts as precursor via a PVP-assisted hydrothermal method

The synthesis of MoS2 nanoparticles from MoO3 with a certain morphology through a surfactant-assisted hydrothermal process is described in this paper. MoO3, which has a nanobelt morphology with a width of 100-500 nm and a length from one to several micrometers, is used as the precursor, and poly(vinylpyrrolidone) (PVP) is used as the surfactant. The morphology of the resulting MoS2 nanomaterial has been characterized by the field-emission scanning electron microscope, which shows that the obtained nanoparticles have diameters ranging from 50 to 100 nm with rough surfaces. Additionally, the composition and crystallinity as well as the phase information of the produced nanoparticles have been characterized by the energy-dispersive X-ray spectrometer and X-ray diffraction. Specifically, in this process, the presence of PVP plays a crucial role for the successful fabrication of the nanoparticle morphology, which may be due to the formation of PVP micelles leading to an oriented aggregation of MoS2 nuclei. In addition, comparative experiments have been conducted and the possible reaction mechanism is proposed. (C) 2016 Elsevier B.V. All rights reserved

Effects of sand burial and overstory tree age on seedling establishment in coastal Pinus thunbergii forests in the northern Shandong Peninsula, China

Coastal Pinus thunbergii (Japanese black pine) forests in the northern Shandong Peninsula of China recently experienced widespread natural regeneration failure. This study identifies critical factors that affect natural regeneration of P. thunbergii. Seeds from trees of various ages (13-32 years) were used to investigate the effects of age and burial depth in sand on germination and seedling establishment. Results show that seed density in 2-5 cm soil decreased with increased distance from the shoreline. Sand burial decreased seed germination but did not affect the relative growth rate of seedlings at depths from 0.5 to 3 cm. Germination, leaf mass ratio, and relative growth rates were higher with seedlings originating from older trees, all of which enhanced seedling resistance to sand burial. Tree age and seed burial were found to be determining factors for natural regeneration of the coastal P. thunbergii forest. Silvicultural treatments that promote quality of seed sources and mitigation of sand burial can be used in the future to improve the regeneration of these coastal forests