LncRNA H19 Promotes Gastric Cancer Metastasis via miR-148-3p/SOX-12 Axis.

Background: Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR-148a-3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR-148a-3p. As expected, miR-148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR-148a-3p is the H19-associated miRNA in GC. We also confirmed that SOX-12 expression was upregulated in GC patient's samples. SOX-12 expression was positively correlated with expression of H19 and was able to directly bind to miR-148a-3p. Importantly, in vitro wound healing assay showed that knockout of SOX-12 could reverse the promoting effect of H19 overexpression on cell migration. Conclusion: In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR-138a-3p/SOX-12 axis.

High Uric Acid Orchestrates Ferroptosis to Promote Cardiomyopathy Via ROS-GPX4 Signaling.

Aims: High uric acid (HUA), as a pro-oxidant, plays a significant role in the pathophysiology of cardiovascular disease. Studies have indicated that elevated uric acid levels can adversely affect cardiovascular health. Nevertheless, the impact of hyperuricemia on cardiomyopathy remains uncertain. Further research is needed to elucidate the relationship between HUA and cardiomyopathy, shedding light on its potential implications for heart health. Results: We demonstrated that uricase knockout (Uox-KO) mice accelerated the development of cardiomyopathy, causing significantly impaired cardiac function and myocardial fibrosis. Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with doxorubicin (DOX) treatment. Benzbromarone, a uric acid-lowering drug, decreases myocardial fibrosis, and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterward, we demonstrated that HUA can promote oxidative stress in DOX, characterized by increased mitochondrial ROS, and downregulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-l-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression. Innovation: We verified that HUA can exacerbate myocardial damage. This has clinical implications for the treatment of cardiac damage in patients with hyperuricemia. Conclusions: Our data suggested that HUA promotes the cardiomyopathy. HUA promotes DOX-induced ferroptosis by increasing oxidative stress and downregulating GPX4. Antioxid. Redox Signal. 00, 00-00.

Impact of Pulmonary Artery Banding in Patients with Congenital Heart Disease and Pulmonary Hypertension.

Background: To evaluate the effectiveness of the surgical approach in patients with congenital heart disease and pulmonary hypertension (PH). Methods: This was a retrospective clinical review of patients with congenital heart disease and PH who underwent pulmonary artery banding (PAB) at our institution between January 2013 and January 2023. Results: We identified 219 patients (53.4% males) with a median age of 7 (4.0-15.0) months and a median weight of 6.8 (5.2-9.0) kg at the time of PAB. The median hospital stay was 7.0 (5.0-10.0) days. The in-hospital mortality rate was 4.6%. The median follow-up was 33.0 (17.0-61.0) months. Survival rates were 96.9 ± 2.5% at 60 months and 92.1 ± 6.9% at 120 months post-PAB. 43.8% of patients had a de-banding procedure, and 147 (79.0%) patients received a second-stage procedure (34.7% univentricular, 65.3% biventricular). The mortality rate between stages was 4.3%. 21 (9.6%) patients reached a third-stage procedure. The overall mortality rate was 9.1%. Conclusions: PAB is an acceptable strategy for patients with congenital heart disease complicated with PH. The results and outcomes of subsequent univentricular or biventricular procedures are generally good.

Age-related alterations in vortex veins on indocyanine green angiography.

To determine age-related alterations in vortex veins in healthy subjects. A total of 228 healthy subjects (aged 4 to 86 years) were recruited and divided into four groups (G1, <21 years; G2, 21-40 years; G3, 41-60 years; and G4, 61-86 years). The clinical characteristics of the participants were recorded, and parameters including the number of vortex vein roots (NVVR), the central vortex vein diameter (CVVD), the mean root area of the vortex vein (MRAVV), and the weighted mean of the thickest branch diameter (WMTBD) were obtained by marking the vortex veins on indocyanine green angiography (ICGA). The NVVR in the age group over 60 years old was significantly lower than that in other age groups (P < 0.05). The CVVD, MRAVV, and WMTBD of all age groups increased with increasing age (P < 0.05). The NVVR was unevenly distributed among the quadrants (P < 0.001). The proportions of type four vortex veins (complete systems including ampulla) and anastomotic branches of the vortex veins were significantly increased in elderly participants over 50 years of age (P < 0.05). Subfoveal choroidal thickness was significantly correlated with age, NVVR, CVVD and MRAVV (P < 0.05). This is the first study to reveal age-related alterations in vortex veins on ICGA in a healthy population. Aging may lead to partial vortex occlusion and residual vortex dilation. As age increases, anastomotic branches increasingly appear between the originally independent vortex veins. Translational relevance: Aging may lead to partial vortex occlusion and residual vortex dilation.

Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer.

BACKGROUND: Several studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. METHODS: Pooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. RESULTS: The median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). CONCLUSION: The differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.

Cannabinoid receptor 2 agonist AM1241 alleviates epileptic seizures and epilepsy-associated depression via inhibiting neuroinflammation in a pilocarpine-induced chronic epilepsy mouse model.

Increasing evidence suggests that cannabinoid receptor 2 (CB2R) serves as a promising anti-inflammatory target. While inflammation is known to play crucial roles in the pathogenesis of epilepsy, the involvement of CB2R in epilepsy remains unclear. This study aimed to investigate the effects of a CB2R agonist, AM1241, on epileptic seizures and depressive-like behaviors in a mouse model of chronic epilepsy induced by pilocarpine. A chronic epilepsy mouse model was established by intraperitoneal administration of pilocarpine. The endogenous cannabinoid system (eCBs) in the hippocampus was examined after status epilepticus (SE). Animals were then treated with AM1241 and compared with a vehicle-treated control group. Additionally, the role of the AMPK/NLRP3 signaling pathway was explored using the selective AMPK inhibitor dorsomorphin. Following SE, CB2R expression increased significantly in hippocampal microglia. Administration of AM1241 significantly reduced seizure frequency, immobility time in the tail suspension test, and neuronal loss in the hippocampus. In addition, AM1241 treatment attenuated microglial activation, inhibited pro-inflammatory polarization of microglia, and suppressed NLRP3 inflammasome activation in the hippocampus after SE. Further, the therapeutic effects of AM1241 were abolished by the AMPK inhibitor dorsomorphin. Our findings suggest that CB2R agonist AM1241 may alleviate epileptic seizures and its associated depression by inhibiting neuroinflammation through the AMPK/NLRP3 signaling pathway. These results provide insight into a novel therapeutic approach for epilepsy.

Facile synthesis of MnO/NC nanohybrids toward high-efficiency ORR for zinc-air battery.

The development of inexpensive non-precious metal materials as high-efficiency stable oxygen reduction reaction (ORR) catalysts holds significant promise for application in metal-air batteries. Here, we synthesized a series of nanohybrids formed from MnO nanoparticles anchored on N-doped Ketjenblack carbon (MnO/NC) via a facile hydrothermal reaction and pyrolysis strategy. We systematically investigated the influence of pyrolysis temperature (600 to 900 °C) on the ORR activities of the MnO/NC samples. At the optimized pyrolysis temperature of 900 °C, the resulting MnO/NC (referred to as MnO/NC-900) exhibited superior ORR activity (onset potential = 0.85 V; half-wave potential = 0.74 V), surpassing other MnO/NC samples and nitrogen-doped Ketjenblack carbon (NC). Additionally, MnO/NC-900 demonstrated better stability than the Pt/C catalyst. The enhanced ORR activity of MnO/NC-900 was attributed to the synergy effect between MnO and NC, abundant surface carbon defects and surface-active components (N species and oxygen vacancies). Notably, the Zinc-air battery (ZAB) equipped MnO/NC-900 as the cathode catalyst delivered promising performance metrics, including a high peak power density of 146.5 mW cm-2, a large specific capacity of 795 mA h gZn -1, and an excellent cyclability up to 360 cycles. These results underscore the potential of this nanohybrid for applications in energy storage devices.

GO/MoS2@PVA composite membrane-based optical fiber Mach-Zehnder interferometer for humidity sensing and its non-contact sensing application.

A humidity sensor based on an optical fiber Mach-Zehnder interferometer (MZI) coated with a GO/MoS2@PVA composite membrane was investigated for non-contact sensing. MoS2 was used as a nanospacer to enhance the humidity-sensitive properties of GO, and the adhesion and stability of the composite membrane on the fiber surface could be increased by PVA. The proposed sensor shows a maximum sensitivity of 0.26 dB/%RH with average response and recovery times of 1.62 and 1.11 s, respectively. In non-contact sensing applications, the sensor can effectively recognize a maximum distance of 10 mm for the proximity of a human finger with a distance variation interval of 3 mm. The proposed sensor is expected to be applied in non-contact distance detection and localization or as a non-contact human-computer interaction panel.

Harmonic phase-sensitive detection for quartz-enhanced photoacoustic-thermoelastic spectroscopy.

Quartz tuning fork (QTF)-based techniques of photoacoustic spectroscopy and thermoelastic spectroscopy play a significant role in trace gas sensing due to unique high sensitivity and compactness. However, the stability of both techniques remains plagued by the inevitable and unpredictable laser power variation and demodulation phase variation. Herein, we investigate the phase change of a QTF when integrating both techniques for enhanced gas sensing. By demonstrating harmonic phase-sensitive methane detection as an example, we achieve stable gas measurement at varying laser power (2.4-9.4 mW) and varying demodulation phase (-90-90°). Besides, this method shows more tolerance to resonant frequency drift, contributing to a small signal fluctuation of ≤ 6.4 % over a wide modulation range (>10 times of the QTF bandwidth). The realization of harmonic-phase detection allows strengthening the stability of QTF-based sensors in a simple manner, especially when stable parameters, such as laser power, demodulation phase, even resonant frequency, cannot always be maintained.

Dysfunction of thalamocortical circuits in early-onset schizophrenia.

Previous studies have demonstrated that the thalamus is involved in multiple functional circuits in participants with schizophrenia. However, less is known about the thalamocortical circuit in the rare subtype of early-onset schizophrenia. A total of 110 participants with early-onset schizophrenia (47 antipsychotic-naive patients) and 70 matched healthy controls were recruited and underwent resting-state functional and diffusion-weighted magnetic resonance imaging scans. A data-driven parcellation method that combined the high spatial resolution of diffusion magnetic resonance imaging and the high sensitivity of functional magnetic resonance imaging was used to divide the thalamus. Next, the functional connectivity between each thalamic subdivision and the cortex/cerebellum was investigated. Compared to healthy controls, individuals with early-onset schizophrenia exhibited hypoconnectivity between subdivisions of the thalamus and the frontoparietal network, visual network, ventral attention network, somatomotor network and cerebellum, and hyperconnectivity between subdivisions of thalamus and the parahippocampal and temporal gyrus, which were included in limbic network. The functional connectivity between the right posterior cingulate cortex and 1 subdivision of the thalamus (region of interest 1) was positively correlated with the general psychopathology scale score. This study showed that the specific thalamocortical dysconnection in individuals with early-onset schizophrenia involves the prefrontal, auditory and visual cortices, and cerebellum. This study identified thalamocortical connectivity as a potential biomarker and treatment target for early-onset schizophrenia.

The proactive and reactive mechanisms of learned spatial suppression.

Selection history refers to the notion that previous allocations of attention or suppression have the potential to elicit lingering and enduring selection biases that are isolated from goal-driven or stimulus-driven attention. However, in the singleton detection mode task, manipulating the selection history of distractors cannot give rise to pure proactive inhibition. Therefore, we employed a combination of a working memory task and a feature search mode task, simultaneously recording cortical activity using EEG, to investigate the mechanisms of suppression guided by selection history. The results from event-related potential and reaction times showed an enhanced inhibitory performance when the distractor was presented at the high-probability location, along with instances where the target appeared at the high-probability location of distractors. These findings demonstrate that a generalized proactive inhibition bias is learned and processed independent of cognitive resources, which is supported by selection history. In contrast, reactive rejection toward the low-probability location was evident through the Pd component under varying cognitive resource conditions. Taken together, our findings indicated that participants learned proactive inhibition when the distractor was at the high-probability location, whereas reactive rejection was involved at low-probability location.

[Combination of acupuncture therapy and kinesiotherapy: an example of pain rehabilitation].

The effect mechanism and the characteristics of clinical application of the combination of acupuncture therapy and kinesiotherapy are explored for pain rehabilitation. Analgesia of acupuncture therapy and kinesiotherapy is characterized by multiple targets and dimensions. The paper summarizes the effect mechanisms of these two therapies and their synergistic action and investigates the current situation and clinical characteristics of their combination in treatment of musculoskeletal pain, visceral pain and postoperative pain so that the references can be provided for the selection of pain rehabilitation programs.

Study on health education methods based on rural residents' infectious disease-specific health literacy in Shandong, China.

Adequate infectious disease-specific health literacy (IDSHL) is of benefit to residents in dealing with infectious diseases. This study aimed to investigate the methods by which residents acquire knowledge about infectious disease prevention and control (IDPC knowledge) so as to find effective health education methods used to improve residents' IDSHL level. In 2022, a cross-sectional study was conducted in Shandong Province, China. Participants were recruited from rural areas by multistage sampling. The IDPC knowledge cognitive questionnaire, as a reliable and valid tool, was applied to data collection and to investigate the participants' IDPC knowledge. Chi-square analysis was utilized to analyze the differences in possession level of IDSHL between different subgroups. The relationship between demographic factors and methods to acquire IDPC knowledge was also examined by chi-square analysis. The possession rate of adequate IDSHL among the total 2283 participants was 31.80%. There was a significant association between IDSHL level and socio-demographic factors, including age (P < .001), sex (P = .02), education (P < .001), occupation (P < .001), annual family income (P < .001), whether to use smartphones (P < .001), whether to browse WeChat on smartphones (P < .001), and whether to browse apps on smartphones except WeChat (P < .001). Univariate analysis showed that whether to adopt specific methods, including television (P = .02), WeChat on smartphones (P < .001), propaganda of infectious disease prevention and control (P < .001), and doctor's advice (P < .001) to acquire IDPC knowledge had significant associations with IDSHL level. Age (P < .001), education (P < .05), occupation (P < .05), and annual family income (P < .01) were associated with methods to acquire IDPC knowledge. The rural residents' adequate IDSHL in Shandong Province, China, was not optimistic. The combination of traditional methods and Internet publicity platforms should take greater responsibility for IDSHL health education among rural populations.

Improved moisture barrier and mechanical properties of rice protein/sodium alginate films for banana and oil preservation: Effect of the type and addition form of fatty acid.

Attenuating the moisture sensitivity of hydrophilic protein/polysaccharide-based films without impairing other properties remains a challenge. Fatty acid dispersed in Pickering emulsion was proposed to overcome such issue. An increase in fatty acid chain length slightly reduced the water vapor permeability (WVP) of emulsion films. As the number of fatty acid double bonds increased from 0 to 1, the WVP of emulsion films was significantly decreased by 14.02% while mechanical properties were significantly enhanced. More hydrogen bonds and stronger electrostatic interactions in the presence of fatty acids were observed by molecular dynamics simulation. The weight loss of bananas coated with oleic acid-incorporated film-forming emulsion was 6.81% lower than that of uncoated group after 4 days, and the corresponding film was more effective to delay oil oxidation than the commercial polypropylene film, indicating that the film is a promising alternative to food coating and packaging material.

Transcriptomic profiling identifies a nucleotide metabolism-related signature with prognostic power in gliomas.

OBJECTIVE: Nucleotide metabolic reprogramming as a hallmark of cancer is closely related to the occurrence and progression of cancer. We aimed to comprehensively analyze the nucleotide metabolism-related gene set and clinical significance in gliomas. METHODS: The RNA sequencing data of 702 gliomas from the Cancer Genome Atlas (TCGA) dataset were included as the training set, and the RNA sequencing data from the other three datasets (CGGA, GSE16011, and Rembrandt) were used as independent validation sets. Survival curve, Cox regression analysis, time-dependent ROC curve and nomogram model were performed to evaluate prognostic power of signature. R language was the main tool for bioinformatic analysis and graphical work. RESULTS: Based on the expression profiles of nucleotide metabolism-related genes, consensus clustering identified two robust clusters with different prognosis. We then developed a nucleotide metabolism-related signature that was closely related to clinical, pathological, and genomic characteristics of gliomas. And ROC curve showed that our signature was a potential biomarker for mesenchymal subtype. Survival curve and Cox regression analysis revealed signature as an independent prognostic factor for gliomas. In addition, we constructed a nomogram model to predict individual survival. Finally, functional analysis showed that nucleotide metabolism not only affected cell division and cell cycle, but also was associated with immune response in gliomas. CONCLUSION: We developed a nucleotide metabolism-related signature to predict prognosis and provided new insights into the role of nucleotide metabolism in gliomas.

Pueraria lobata-Prunus mume Complex Alleviates Alcoholic Liver Disease by Regulating Lipid Metabolism and Inhibiting Inflammation: A Transcriptome and Gut Microbiota Analysis.

BACKGROUND: Lipid metabolism disorder appears to be one of the early features of alcoholic liver disease (ALD), which can be speculated via omics analysis including liver transcriptomics and gut microbiota. A complex consisting of the roots of Pueraria lobata and dried fruits of Prunus mume (PPC), which possesses hepatoprotective effects, could serve as a drug or functional food. The lack of non-polysaccharide compounds in PPC with their moderation effects on gut microbiota suggests the necessity for a relevant study. METHODS: Six groups of Kunming mice (control, Baijiu injury, silybin, low, medium, and high) were modelled by gavage with Baijiu (for 14 days) and PPC (equivalent to a maximum dose of 9 g/kg in humans). The liver transcriptome data were analyzed to predict gene annotation, followed by the verification of gut microbiota, serum, tissue staining, immunohistochemistry, and Western blotting. Liquid chromatography-mass spectrometry was used to detect the components. RESULTS: PPC normalized serum ALT (40 U/L), down-regulated TLR4-NF-κB signaling pathway to inhibit the release of TNF-α (90 pg/mL), improved the expression of occludin, claudin-4, and ZO-1, and restored the abundance of Muribaculaceae, Bacteroides and Streptococcus. CONCLUSION: PPC can alleviate ALD by regulating the gut microbiota with an anti-inflammatory and intestinal barrier, and has an application value in developing functional foods.

A Density Clustering RAPID Based on an Array-Compensated Damage Index for Quantitative Damage Diagnosis.

Guided wave array-based structural health monitoring (SHM) is a promising solution for diagnosing damage in metal-connected structures. In this field, the reconstruction algorithm for probabilistic inspection (RAPID) is one of the most widely used algorithms for performing damage localization. In this paper, a density clustering RAPID based on an array-compensated damage index is proposed. A new probability distribution function was constructed based on a new damage index, which is adaptive to different elements in the sensor array to compensate for performance variation. Then, the imaging matrix of the RAPID algorithm was density-clustered to obtain the location and degree of damage. Finally, the method was verified by experiments on a stiffened aluminum plate. The experimental results demonstrate that the method achieves damage localization and enables quantitative damage diagnosis.

Morphological, Physiological, and Photosynthetic Differences of Tartary Buckwheat Induced by Post-Anthesis Drought.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is a crop of significant interest due to its nutritional value and resilience to drought conditions. However, drought, particularly following flowering, is a major factor contributing to yield reduction. This research employed two distinct Tartary buckwheat genotypes to investigate the effects of post-anthesis drought on growth and physicochemical characteristics. The study aimed to elucidate the response of Tartary buckwheat to drought stress. The findings indicated that post-anthesis drought adversely impacted the growth, morphology, and biomass accumulation of Tartary buckwheat. Drought stress enhanced the maximum photosynthetic capacity (Fv/Fm) and light protection ability (NPQ) of the 'Xiqiao-2' genotype. In response to drought stress, 'Dingku-1' and 'Xiqiao-2' maintained osmotic balance by accumulating soluble sugars and proline, respectively. Notably, 'Xiqiao-2' exhibited elevated levels of flavonoids and polyphenols in its leaves, which helped mitigate oxidative damage caused by drought. Furthermore, rewatering after a brief drought period significantly improved plant height, stem diameter, and biomass accumulation in 'Dingku-1'. Overall, 'Xiqiao-2' demonstrated greater long-term tolerance to post-anthesis drought, while 'Dingku-1' was less adversely affected by short-term post-anthesis drought.

The computational and neural substrates of individual differences in impulsivity under loss framework.

Numerous neuroimaging studies have identified significant individual variability in intertemporal choice, often attributed to three neural mechanisms: (1) increased reward circuit activity, (2) decreased cognitive control, and (3) prospection ability. These mechanisms that explain impulsivity, however, have been primarily studied in the gain domain. This study extends this investigation to the loss domain. We employed a hierarchical Bayesian drift-diffusion model (DDM) and the inter-subject representational similarity approach (IS-RSA) to investigate the potential computational neural substrates underlying impulsivity in loss domain across two experiments (n = 155). These experiments utilized a revised intertemporal task that independently manipulated the amounts of immediate and delayed-loss options. Behavioral results demonstrated positive correlations between the drift rate, measured by the DDM, and the impulsivity index K in Exp. 1 (n = 97) and were replicated in Exp. 2 (n = 58). Imaging analyses further revealed that the drift rate significantly mediated the relations between brain properties (e.g., prefrontal cortex activations and gray matter volume in the orbitofrontal cortex and precuneus) and K in Exp. 1. IS-RSA analyses indicated that variability in the drift rate also mediated the associations between inter-subject variations in activation patterns and individual differences in K. These findings suggest that individuals with similar impulsivity levels are likely to exhibit similar value processing patterns, providing a potential explanation for individual differences in impulsivity within a loss framework.

High-throughput identification of functional regulatory SNPs in systemic lupus erythematosus.

Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift and luciferase reporter assays. To validate the approach, we studied rs2297550 in detail, finding that the risk allele enhanced binding to the transcription factor Ikaros (encoded by IKZF1), thereby modulating expression of IKBKE. Correspondingly, primary cells from genotyped healthy donors bearing the risk allele expressed higher levels of the interferon / NF-κB regulator IKKε. Together, these findings define a set of likely functional non-coding lupus risk variants and identify a regulatory pathway involving rs2297550, Ikaros, and IKKε implicated by human genetics in risk for SLE.