B Cell-Related Circulating MicroRNAs With the Potential Value of Biomarkers in the Differential Diagnosis, and Distinguishment Between the Disease Activity and Lupus Nephritis for Systemic Lupus Erythematosus

Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls (P < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients (P < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity (P < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) (P < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN

Demonstrating a superconducting dual-rail cavity qubit with erasure-detected logical measurements

A critical challenge in developing scalable error-corrected quantum systems is the accumulation of errors while performing operations and measurements. One promising approach is to design a system where errors can be detected and converted into erasures. A recent proposal aims to do this using a dual-rail encoding with superconducting cavities. In this work, we implement such a dual-rail cavity qubit and use it to demonstrate a projective logical measurement with erasure detection. We measure logical state preparation and measurement errors at the $0.01\%$-level and detect over $99\%$ of cavity decay events as erasures. We use the precision of this new measurement protocol to distinguish different types of errors in this system, finding that while decay errors occur with probability $\sim 0.2\%$ per microsecond, phase errors occur 6 times less frequently and bit flips occur at least 170 times less frequently. These findings represent the first confirmation of the expected error hierarchy necessary to concatenate dual-rail erasure qubits into a highly efficient erasure code

Does the Development of a High-Speed Railway Improve the Equalization of Medical and Health Services? Evidence from China

Does the development of a high-speed railway (HSR) have a significant impact on the equalization of medical and health resources allocated among cities? Based on the panel data of 67 cities in China from 2007 to 2016, this paper investigates the direct and dynamic effects of HSR development on the equalization of medical and health services by using the difference-in-differences (DID) method. The empirical results show that an HSR connection significantly reduces the equalization level of medical and health services in cities and that the effect is larger for the period from the year of the connection to the second year. However, in the long term, HSR development improves the equalization level of medical and health services in cities. Heterogeneity tests show that the effect of the HSR connection shows an “N”-shaped trend under different city scales, the equalization level of medical resources in the largest cities benefit the most from HSR development, and the Eastern and Western regions of China are more sensitive to the HSR connection. While the allocation of medical resources is in the direction of equalization, the level of medical resources is significantly more equal with the HSR development in cities with stronger financial capacity and non-core cities. The analysis of other city characteristics provides policy recommendations for improving the public services delivery mode in China’s heterogeneous cities in terms of HSR development

NovelmiRNA-25 inhibits AMPD2 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus and represents a promising novel biomarker

Abstract Background Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with various clinical manifestations. MicroRNAs (miRNAs) and immunometabolism are recognized as key elements in SLE pathogenesis; however, the relationship between miRNAs in peripheral blood mononuclear cells (PBMCs) and metabolism in SLE remains unclear. Methods We detected PBMC miRNA and mRNA profiles from 3 pooled SLE patients and 3 healthy controls (HCs) using next-generation sequencing, predicted miRNA targets in dysregulated mRNAs, predicted functions and interactions of differentially expressed genes using bioinformatics analysis, validated candidate miRNAs using qRT-PCR, and investigated the association between the expression of candidate miRNAs and SLE clinical characteristics. Moreover, we validated the direct and transcriptional regulatory effect of NovelmiRNA-25 on adenosine monophosphate deaminase 2 (AMPD2) using a dual-luciferase reporter assay and western blot and confirmed AMPD2 mRNA and protein expression in PBMCs using qRT-PCR and western blot, respectively. Results Multilayer integrative analysis of microRNA and mRNA regulation showed that 10 miRNAs were down-regulated and 19 miRNAs were up-regulated in SLE patient PBMCs compared with HCs. Bioinformatics analysis of regulatory networks between miRNAs and mRNAs showed that 19 miRNAs were related to metabolic processes. Two candidate miRNAs, NovelmiRNA-25 and miR-1273h-5p, which were significantly increased in the PBMCs of SLE patients (P < 0.05), represented diagnostic biomarkers with sensitivities of 94.74% and 89.47%, respectively (area under the curve = 0.574 and 0.788, respectively). NovelmiRNA-25 expression in PBMCs was associated with disease activity in SLE patients, in both active and stable groups (P < 0.05). NovelmiRNA-25 overexpression downregulated AMPD2 expression in HEK293T cells through direct targeting of the AMPD2 3ʹUTR (P < 0.01), while inhibition of NovelmiRNA-25 activity led to increased AMPD2 expression (P < 0.01). NovelmiRNA-25 overexpression also downregulated AMPD2 protein expression in HEK293T cells; AMPD2 protein expression in SLE patient PBMCs was decreased. Our results show that differentially expressed miRNAs play an important role in SLE. Conclusions Our data demonstrate a novel mechanism in SLE development that involves the targeting of AMPD2 expression by NovelmiRNA-25. miRNAs may serve as novel biomarkers for the diagnosis and evaluation of disease activity of SLE and represent potential therapeutic targets for this disease

Geographic Variations in Dietary Patterns and Their Associations with Overweight/Obesity and Hypertension in China: Findings from China Nutrition and Health Surveillance (2015–2017)

Regional dietetic cultures were indicated in China, but how dietary patterns geographically varied across China is unknown. Few studies systematically investigated the association of dietary patterns with overweight/obesity and hypertension and the potential mechanism with a national sample. This study included 34,040 adults aged 45 years and older from China Nutrition and Health Surveillance (2015–2017), who had complete outcome data, reliable intakes of calorie and cooking oils, unchanged diet habits, and without diagnosed cancer or cardiovascular disease. Outcomes were overweight/obesity and hypertension. By using the Gaussian finite mixture models, four dietary patterns were identified—common rice-based dietary pattern (CRB), prudent diversified dietary pattern (PD), northern wheat-based dietary pattern (NWB), and southern rice-based dietary pattern (SRB). Geographic variations in dietary patterns were depicted by age–sex standardized proportions of each pattern across 31 provinces in China. We assessed the association of these dietary patterns with outcomes and calculated the proportion mediated (PM) by overweight/obesity in the association of the dietary patterns with hypertension. Evident geographic disparities in dietary patterns across 31 provinces were observed. With CRB as reference group and covariates adjusted, the NWB had higher odds of being overweight/obese (odds ratio (OR) = 1.44, 95% confidence interval (CI): 1.36–1.52, p p p p = 0.038 for SRB and p < 0.001 for PD, PMs = 27.8% and 9.9%). The highest risk of overweight/obesity in the NWB presented in relatively higher carbohydrate intake (about 60% of energy) and relatively low fat intake (about 20% of energy). The different trends in the association of protein intake with overweight/obesity among dietary patterns were related to differences in animal food sources. In conclusion, the geographic distribution disparities of dietary patterns illustrate the existence of external environment factors and underscore the need for geographic-targeted dietary actions. Optimization of the overall dietary pattern is the key to the management of overweight/obesity and hypertension in China, with the emphasis on reducing low-quality carbohydrate intake, particularly for people with the typical northern diet, and selection of animal foods, particularly for people with the typical southern diet