Assessing parameter efficient methods for pre-trained language model in annotating scRNA-seq data.

Annotating cell types of single-cell RNA sequencing (scRNA-seq) data is crucial for studying cellular heterogeneity in the tumor microenvironment. Recently, large-scale pre-trained language models (PLMs) have achieved significant progress in cell-type annotation of scRNA-seq data. This approach effectively addresses previous methods' shortcomings in performance and generalization. However, fine-tuning PLMs for different downstream tasks demands considerable computational resources, rendering it impractical. Hence, a new research branch introduces parameter-efficient fine-tuning (PEFT). This involves optimizing a few parameters while leaving the majority unchanged, leading to substantial reductions in computational expenses. Here, we utilize scBERT, a large-scale pre-trained model, to explore the capabilities of three PEFT methods in scRNA-seq cell type annotation. Extensive benchmark studies across several datasets demonstrate the superior applicability of PEFT methods. Furthermore, downstream analysis using models obtained through PEFT showcases their utility in novel cell type discovery and model interpretability for potential marker genes. Our findings underscore the considerable potential of PEFT in PLM-based cell type annotation, presenting novel perspectives for the analysis of scRNA-seq data.

ANCA-associated systemic vasculitis initially mimicking peripheral neuropathy in an elderly woman.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) is a rare systemic immunological condition that predominantly impacts small arteries, veins, and capillaries, often leading to kidney damage and pulmonary injury. It is important to note that individuals primarily presenting with peripheral neuropathy (PN) are uncommon in AASV, which can result in significant misdiagnosis or undiagnosed cases. The severity and location of PN can vary among patients. In this article, we present a case of an AASV patient initially showing signs of PN. This case highlights the significance of considering AASV as a potential cause of unexplained neurological symptoms. Timely identification and proper treatment are essential for improving the survival rate and functional prognosis of AASV patients.

Overexpression of microRNA-93-5p and microRNA-374a-5p Suppresses the Osteogenic Differentiation and Mineralization of Human Aortic Valvular Interstitial Cells Through the BMP2/Smad1/5/RUNX2 Signaling Pathway.

ABSTRACT: Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate-induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium-phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.

Effects of home-based telehealth on the physical condition and psychological status of patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIMS: This systematic review and meta-analysis aimed to evaluate the effects of home-based telehealth compared with usual care on six-minute walking distance (6MWD), health-related quality of life, anxiety and depression in patients with chronic obstructive pulmonary disease. METHODS: We identified randomized controlled trials through a systematic multidatabase search. Titles and abstracts were assessed for relevance. Two authors independently extracted data and assessed the risk of bias and quality of evidence. Meta-analyses were conducted using Review Manager and Stata. RESULTS: We included 32 randomized controlled trials (n = 5232). Devices used for home-based telehealth interventions included telephones, videos, and combined devices. The quality of the evidence was downgraded due to high risk of bias, imprecision, and inconsistency. Home-based telehealth significantly increased 6MWD by 35 m (SD = 30.42) and reduced symptom burden by 3 points (SD = -2.30) on the COPD assessment test compared with usual care. However, no significant differences in anxiety and depression were noted between the home-based telehealth group and the standard care group. In subgroup analysis, home-based telehealth significantly improved 6MWD and health status after 6-12 months and >12 months. CONCLUSION: Low quality evidence showed that home-based telehealth interventions reduce symptom burden and increase walking distance to a clinically meaningful extent in patients with COPD. However, no effects on depression and anxiety were observed.

WDR62 is involved in spindle assembly by interacting with CEP170 in spermatogenesis.

WDR62 is the second most common genetic alteration associated with microcephaly. It has been shown that Wdr62 is required for germ cell meiosis initiation in mice, and the majority of male germ cells are lost in the meiotic defect of first wave spermatogenesis in Wdr62 mutants. Strikingly, in this study, we found that the initiation of meiosis following spermatogenesis was not affected and the germ cells were gradually repopulated at later developmental stages. However, most germ cells were arrested at metaphase of meiosis I and no mature sperm were detected in epididymides. Further, this study demonstrated that metaphase I arrest of Wdr62-deficient spermatocytes was caused by asymmetric distribution of the centrosome and aberrant spindle assembly. Also, mechanistic studies demonstrated that WDR62 interacts with centrosome-associated protein CEP170, and deletion of Wdr62 causes downregulation of the CEP170 protein, which in turn leads to the aberrant spindle assembly. In summary, this study indicates that the meiosis of first wave spermatogenesis and the following spermatogenesis started from spermatogonium is probably regulated by different mechanisms. We also demonstrated a new function of WDR62 in germ cell meiosis, through its interaction with CEP170.

Microfluidic Organs-on-a-Chip for Modeling Human Infectious Diseases.

Infectious diseases present tremendous challenges to human progress and public health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) pandemic continue to pose an imminent threat to humanity. These infectious diseases highlight the importance of developing innovative strategies to study disease pathogenesis and protect human health. Although conventional in vitro cell culture and animal models are useful in facilitating the development of effective therapeutics for infectious diseases, models that can accurately reflect human physiology and human-relevant responses to pathogens are still lacking. Microfluidic organs-on-a-chip (organ chips) are engineered microfluidic cell culture devices lined with living cells, which can resemble organ-level physiology with high fidelity by rebuilding tissue-tissue interfaces, mechanical cues, fluidic flow, and the biochemical cellular microenvironment. They present a unique opportunity to bridge the gap between in vitro experimental models and in vivo human pathophysiology and are thus a promising platform for disease studies and drug testing. In this Account, we first introduce how recent progress in organ chips has enabled the recreation of complex pathophysiological features of human infections in vitro. Next, we describe the progress made by our group in adopting organ chips and other microphysiological systems for the study of infectious diseases, including SARS-CoV-2 viral infections and intrauterine bacterial infections. Respiratory symptoms dominate the clinical manifestations of many COVID-19 patients, even involving the systemic injury of many distinct organs, such as the lung, the gastrointestinal tract, and so forth. We thus particularly highlight our recent efforts to explore how lung-on-a-chip and intestine-on-a-chip might be useful in addressing the ongoing viral pandemic of COVID-19 caused by SARS-CoV-2. These organ chips offer a potential platform for studying virus-host interactions and human-relevant responses as well as accelerating the development of effective therapeutics against COVID-19. Finally, we discuss opportunities and challenges in the development of next-generation organ chips, which are urgently needed for developing effective and affordable therapies to combat infectious diseases. We hope that this Account will promote awareness about in vitro organ microphysiological systems for modeling infections and stimulate joint efforts across multiple disciplines to understand emerging and re-emerging pandemic diseases and rapidly identify innovative interventions.

Cockroaches adjust body and appendages to traverse cluttered large obstacles.

To traverse complex terrain, animals often transition between locomotor modes. It is well known that locomotor transitions can be induced by switching in neural control circuits or driven by a need to minimize metabolic energetic cost. Recent work revealed that locomotor transitions in complex 3D terrain cluttered with large obstacles can emerge from physical interaction with the environment controlled by the nervous system. For example, to traverse cluttered, stiff grass-like beams, the discoid cockroach often transitions from using a strenuous pitch mode pushing across the beams to using a less strenuous roll mode rolling into and through the gaps. This transition can save mechanical energetic cost substantially (∼100-101 mJ) but requires overcoming a potential energy barrier (∼10-3-10-2 mJ). Previous robotic physical modeling demonstrated that kinetic energy fluctuation of body oscillation from self-propulsion can help overcome the barrier and facilitate this transition. However, the animal was observed to transition even when the barrier still exceeded kinetic energy fluctuation. Here, we further studied whether and how the cockroach makes active adjustments to facilitate this transition to traverse cluttered beams. The animal repeatedly flexed its head and abdomen, reduced hindleg sprawl, and depressed one hindleg and elevated the other during the pitch-to-roll transition, adjustments which were absent when running on a flat ground. Using a refined potential energy landscape with additional degrees of freedom to model these adjustments, we found that head flexion did not substantially reduce the transition barrier (by ∼10-3 mJ), whereas leg sprawl reduction did so dramatically (by ∼10-2 mJ). We speculate that head flexion is for sensing the terrain to guide the transition via sensory feedback control.

Heavy metal pollution in a black shale post-mining site of southern China: Pollution pattern, source apportionment and health risk assessment.

Source apportionment is critical but remains largely unknown for heavy metals in the soil surrounding black shale mining areas. Herein, the distribution, potential hazards, and sources of heavy metals in the soil around a black shale post-mining site were investigated. The content of Cadmium (Cd) in topsoil samples (0.77-50.29 mg/kg, N = 84) all exceeded the Chinese agricultural soil standard (0.3 mg/kg). The majority of Cd in the soil existed in the mobile fraction posing a high potential risk to the local ecosystem. and Zn and V in soils existed in the residual form. The percentages of HQing > 1 and 0.6-1 for Vanadium (V) in soil were 8.3% and 31.0%, respectively, and the percentages of HQing > 0.5 for Cd in soil were 3.7% showed that V and Cd were the main factors that increased the potential non-cancer risk. Five potential sources were identified using the geostatistical and positive matrix factorization (PMF) model, among which Cd was mainly derived from the short-term weathering process of black shale (81.06%), most Zinc (Zn) was from the long-term weathering of black shale (67.35%), whereas V was contributed by many factors including long-term weathering of black shale (42.99%), traffic emissions (31.12%) and agricultural activities (21.05%). This study reveals the potential risk and identifies the sources of heavy metals, which is helpful to manage the contaminated soil in black shale mining areas.

Correction: Wdr62 is involved in female meiotic initiation via activating JNK signaling and associated with POI in humans.

[This corrects the article DOI: 10.1371/journal.pgen.1007463.].

Maximizing Average Throughput of Cooperative Cognitive Radio Networks Based on Energy Harvesting.

Energy harvesting (EH) and cooperative communication techniques have been widely used in cognitive radio networks. However, most studies on throughput in energy-harvesting cooperative cognitive radio networks (EH-CCRNs) are end-to-end, which ignores the overall working state of the network. For the above problems, under the premise of prioritizing the communication quality of short-range users, this paper focuses on the optimization of the EH-CCRN average throughput, with energy and transmission power as constraints. The formulated problem was an unsolved non-deterministic polynomial-time hardness (NP-hard) problem. To make it tractable to solve, a multi-user time-power resource allocation algorithm (M-TPRA) is proposed, which is based on sub-gradient descent and unary linear optimization methods. Simulation results show that the M-TPRA algorithm can improve the average throughput of the network. In addition, the energy consumed by executing the M-TPRA algorithm is analyzed.

Atomic force microscopy-based characterization of the interaction of PriA helicase with stalled DNA replication forks.

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA-binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

Locomotor transitions in the potential energy landscape-dominated regime.

To traverse complex three-dimensional terrain with large obstacles, animals and robots must transition across different modes. However, the most mechanistic understanding of terrestrial locomotion concerns how to generate and stabilize near-steady-state, single-mode locomotion (e.g. walk, run). We know little about how to use physical interaction to make robust locomotor transitions. Here, we review our progress towards filling this gap by discovering terradynamic principles of multi-legged locomotor transitions, using simplified model systems representing distinct challenges in complex three-dimensional terrain. Remarkably, general physical principles emerge across diverse model systems, by modelling locomotor-terrain interaction using a potential energy landscape approach. The animal and robots' stereotyped locomotor modes are constrained by physical interaction. Locomotor transitions are stochastic, destabilizing, barrier-crossing transitions on the landscape. They can be induced by feed-forward self-propulsion and are facilitated by feedback-controlled active adjustment. General physical principles and strategies from our systematic studies already advanced robot performance in simple model systems. Efforts remain to better understand the intelligence aspect of locomotor transitions and how to compose larger-scale potential energy landscapes of complex three-dimensional terrains from simple landscapes of abstracted challenges. This will elucidate how the neuromechanical control system mediates physical interaction to generate multi-pathway locomotor transitions and lead to advancements in biology, physics, robotics and dynamical systems theory.

MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis.

Mutations of WD repeat domain 62 (WDR62) lead to autosomal recessive primary microcephaly (MCPH), and down-regulation of WDR62 expression causes the loss of neural progenitor cells (NPCs). However, how WDR62 is regulated and hence controls neurogenesis and brain size remains elusive. Here, we demonstrate that mitogen-activated protein kinase kinase kinase 3 (MEKK3) forms a complex with WDR62 to promote c-Jun N-terminal kinase (JNK) signaling synergistically in the control of neurogenesis. The deletion of Mekk3, Wdr62, or Jnk1 resulted in phenocopied defects, including premature NPC differentiation. We further showed that WDR62 protein is positively regulated by MEKK3 and JNK1 in the developing brain and that the defects of wdr62 deficiency can be rescued by the transgenic expression of JNK1. Meanwhile, WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. Our findings demonstrate that the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development.

Evaluation of hepatic drug-metabolism for glioblastoma using liver-brain chip.

Glioma is one of the most aggressive and highly fatal diseases with an extremely poor prognosis. Considering the poor clinical response to therapy in glioma, it is urgent to establish an in vitro model to facilitate the screening and assessment of anti-brain-tumor drugs. The blood-brain barrier (BBB), as well as liver metabolism plays an important role in determining the pharmacological activity of many anti-brain-tumor drugs. In this work, we designed a multi-interface liver-brain chip integrating co-culture system to assess hepatic metabolism dependent cytotoxicity of anti-brain-tumor drug in vitro. This microdevice composed of three microchannels which were separated by porous membrane and collagen. HepG2 and U87 cells were cultured in separated channels as mimics of liver and glioblastoma. Brain microvascular endothelial cells (BMECS) and cerebral astrocytes were co-cultured on collagen to mimic the brain microvascular endothelial barrier. Three common anti-tumor drugs, paclitaxel (PTX), capecitabine (CAP) and temozolomide (TMZ), were evaluated on this chip. In integrated liver-brain chip, liver enhanced the cytotoxicity of CAP on U87 cells by 30%, but having no significant effect on TMZ. The BBB decreased the cytotoxicity of PTX by 20%, while no significant effects were observed on TMZ and CAP, indicating the importance of liver metabolism and blood-brain barrier on the evaluation of anti-brain-tumor drugs. This work provides a biomimetic liver-brain model to mimic the physiological and pharmacological processes in vitro and presents a simple platform for long-term cell co-culture, drug delivery and metabolism, and real-time analysis of drug effects on brain cancer.

Wdr62 is involved in female meiotic initiation via activating JNK signaling and associated with POI in humans.

Meiosis is a germ cell-specific division that is indispensable for the generation of haploid gametes. However, the regulatory mechanisms of meiotic initiation remain elusive. Here, we report that the Wdr62 (WD40-repeat protein 62) is involved in meiotic initiation as a permissive factor rather than an instructive factor. Knock-out of this gene in a mouse model resulted in female meiotic initiation defects. Further studies demonstrated that Wdr62 is required for RA-induced Stra8 expression via the activation of JNK signaling, and the defects in meiotic initiation from Wdr62-deficient female mice could be partially rescued by JNK1 overexpression in germ cells. More importantly, two novel mutations of the WDR62 gene were detected in patients with premature ovarian insufficiency (POI), and these mutations played dominant-negative roles in regulating Stra8 expression. Hence, this study revealed that Wdr62 is involved in female meiotic initiation via activating JNK signaling, which displays a novel mechanism for regulating meiotic initiation, and mutation of WDR62 is one of the potential etiologies of POI in humans.

cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development.

Normal neural development is essential for the formation of neuronal networks and brain function. Cutaneous T cell lymphoma-associated antigen 5 (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the secretion of proteins. However, its roles in the transport of nonsecretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is important for brain development and function. Conditional knockout of cTAGE5/MEA6 in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, spine formation and maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects in COPII vesicle formation and transport from the endoplasmic reticulum to the Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines but also the signaling pathways required for neuronal development. Because mutations in cTAGE5/MEA6 have been found in patients with Fahr's disease, our study potentially also provides insight into the pathogenesis of this disorder.

Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression.

Supporting cells (Sertoli and granulosa) and steroidogenic cells (Leydig and theca-interstitium) are two major somatic cell types in mammalian gonads, but the mechanisms that control their differentiation during gonad development remain elusive. In this study, we found that deletion of Wt1 in the ovary after sex determination caused ectopic development of steroidogenic cells at the embryonic stage. Furthermore, differentiation of both Sertoli and granulosa cells was blocked when Wt1 was deleted before sex determination and most genital ridge somatic cells differentiated into steroidogenic cells in both male and female gonads. Further studies revealed that WT1 repressed Sf1 expression by directly binding to the Sf1 promoter region, and the repressive function was completely abolished when WT1 binding sites were mutated. This study demonstrates that Wt1 is required for the lineage specification of both Sertoli and granulosa cells by repressing Sf1 expression. Without Wt1, the expression of Sf1 was upregulated and the somatic cells differentiated into steroidogenic cells instead of supporting cells. Our study uncovers a novel mechanism of somatic cell differentiation during gonad development.

MeSHProbeNet: a self-attentive probe net for MeSH indexing.

MOTIVATION: MEDLINE is the primary bibliographic database maintained by National Library of Medicine (NLM). MEDLINE citations are indexed with Medical Subject Headings (MeSH), which is a controlled vocabulary curated by the NLM experts. This greatly facilitates the applications of biomedical research and knowledge discovery. Currently, MeSH indexing is manually performed by human experts. To reduce the time and monetary cost associated with manual annotation, many automatic MeSH indexing systems have been proposed to assist manual annotation, including DeepMeSH and NLM's official model Medical Text Indexer (MTI). However, the existing models usually rely on the intermediate results of other models and suffer from efficiency issues. We propose an end-to-end framework, MeSHProbeNet (formerly named as xgx), which utilizes deep learning and self-attentive MeSH probes to index MeSH terms. Each MeSH probe enables the model to extract one specific aspect of biomedical knowledge from an input article, thus comprehensive biomedical information can be extracted with different MeSH probes and interpretability can be achieved at word level. MeSH terms are finally recommended with a unified classifier, making MeSHProbeNet both time efficient and space efficient. RESULTS: MeSHProbeNet won the first place in the latest batch of Task A in the 2018 BioASQ challenge. The result on the last test set of the challenge is reported in this paper. Compared with other state-of-the-art models, such as MTI and DeepMeSH, MeSHProbeNet achieves the highest scores in all the F-measures, including Example Based F-Measure, Macro F-Measure, Micro F-Measure, Hierarchical F-Measure and Lowest Common Ancestor F-measure. We also intuitively show how MeSHProbeNet is able to extract comprehensive biomedical knowledge from an input article.

The presence of P2RX7 single nuclear polymorphism is associated with a gain of function in P2X7 receptor and inflammasome activation in SLE complicated with pericarditis.

OBJECTIVES: A case control study was conducted to evaluate the possible influence of P2RX7 single nuclear polymorphism and P2X7 receptor activity in the susceptibility of SLE with pericarditis in Chinese Han population. METHODS: We studied a cohort of SLE patients with (SLE+PCS) or without (SLE-PCS) history of pericarditis and demographic, therapeutic and clinical data were retrospectively collected. P2RX7 489 C>T (His155Tyr) genotype of each subject was analysed and classified as CC or C>T (CT and TT) variant. After isolation of peripheral blood mononuclear cells and macrophages from whole blood by centrifugation on Ficoll gradient, in vitro macrophage releases of IL-1ß and IL-18 primed by LPS were evaluated by cytometric bead array. NLRP3 expression were evaluated by western blot after normalisation of house-keeping gene α-Tubulin. Finally, P2X7 receptor activity was analysed after stimulation with agonist ATP, by measuring permeability changes using ethidium bromide (EB) uptake fluorescent probe. The Hardy-Weinberg Equilibrium (HWE) analysis was used to detect the association of P2RX7 489C>T SNP with SLE complicated with pericarditis. Spearman linear regression analysis was performed to evaluate the association of macrophages uptake of EB and NLRP3 expression. RESULTS: In total 68 SLE+PCS patients and 72 SLE-PCS patients from the cohort were enrolled. No significant differences in demographic, disease activity and serological features were found between the two subgroups. The HWE analysis detected a significant positive association between SLE+PCS and the 489 C>T SNP (OR=0.65, 95%CI (0.46-0.92), p=0.03). No association was found in SLE-PCS patients carrying either genotype CC or C>T. It was shown that in vitro inflammasome-dependent IL-1ß/IL-18 release from macrophages was higher in SLE+PCS patients compared to SLE-PCS, especially in those bearing the C>T variant genotype, and consequently the WB analysis ofNLRP3 expression in SLE+PCS patients bearing C>T genotype was significantly higher compared to the other genotype carriers (F=13.1, p<0.01). We also detected that macrophages of SLE+PCS patients carrying SNP 489C>T showed a higher EB uptake in response to ATP than subjects carrying wild type (CC). The Spearman linear regression analysis showed a significant association of macrophages EB uptake and NLRP3 expression as well as its dependent IL-1ß and IL-18 in SLE+PCS subjects carrying SNP 489 C>T. CONCLUSIONS: Our results suggest that 489 C>T polymorphism of the P2RX7 gene is associated with activation of inflammasome NLRP3 and an increased release of IL-1ß and IL-18. The EB uptake increase in macrophages of LE+PCS subjects carrying 489C>T displays the functional upregulation of P2RX7, which may be involved in the pathogenesis of SLE complicated with pericarditis in the presence of P2RX7 SNP 489C>T.

Ionicity of deep eutectic solvents by Walden plot and pulsed field gradient nuclear magnetic resonance (PFG-NMR).

Deep eutectic solvents (DESs) have attracted considerable attention due to their unique properties. Owing to similar structures and properties, DESs are also called "quasi-ionic liquids" or "ionic liquid analogous". However, for a deeper understanding and application of DESs, a comprehensive investigation on the ionicity of DESs is crucial. In this work, the effects of the structure and components of typical DESs on the ionicity were investigated. Moreover, the ionicity was discussed by using Walden plot, and the validity of applying it to DESs was verified using pulsed field gradient nuclear magnetic resonance (PFG-NMR). We found that the lack of free charged species and high viscosities make it difficult to achieve optimal conductivities for DESs, and thus most of them exhibit "poor ionic" nature. Fortunately, with an in-depth understanding of its microstructure and physicochemical properties, the properties of DESs can be finely tailored by selecting or even designing suitable parent compounds for functional applications. In particular, the ionicity of Li-based DESs was investigated for their potential application as electrolytes in Li-ion batteries.