Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers.

BACKGROUND: Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including cardiovascular complications, suggesting similar underlying immunopathogenic processes. Aberrant neutrophil activation may play a crucial role in the shared pathologies of KD and MIS-C; however, the associated pathogenic mechanisms and molecular drivers remain unknown. METHODS: We performed a single-cell meta-analysis of neutrophil activation with 103 pediatric single-cell transcriptomic peripheral blood mononuclear cell data across 9 cohorts, including healthy controls, KD, MIS-C, compared with dengue virus infection, juvenile idiopathic arthritis, and pediatric celiac disease. We used a series of computational analyses to investigate the shared neutrophil transcriptional programs of KD and MIS-C that are linked to systemic damage and cardiac pathologies, and suggested Food and Drug Administration-approved drugs to consider as KD and MIS-C treatment. RESULTS: We meta-analyzed 521 950 high-quality cells. We found that blood signatures associated with risks of cardiovascular events are enriched in neutrophils of KD and MIS-C. We revealed the expansion of CD177+ neutrophils harboring hyperactivated effector functions in both KD and MIS-C, but not in healthy controls or in other viral-, inflammatory-, or immune-related pediatric diseases. KD and MIS-C CD177+ neutrophils had highly similar transcriptomes, marked by conserved signatures and pathways related to molecular damage. We found the induction of a shared neutrophil expression program, potentially regulated by SPI1 (Spi-1 proto-oncogene), which confers enhanced effector functions, especially neutrophil degranulation. CD177 and shared neutrophil expression program expressions were associated with acute stages and attenuated during KD intravenous immunoglobulin treatment and MIS-C recovery. Network analysis identified hub genes that correlated with the high activation of CD177+ neutrophils. Disease-gene association analysis revealed that the KD and MIS-C CD177+ neutrophils' shared expression program was associated with the development of coronary and myocardial disorders. Last, we identified and validated TSPO (translocator protein) and S100A12 (S100 calcium-binding protein A12) as main molecular targets, for which the Food and Drug Administration-approved drugs methotrexate, zaleplon, metronidazole, lorazepam, clonazepam, temazepam, and zolpidem, among others, are primary candidates for drug repurposing. CONCLUSIONS: Our findings indicate that CD177+ neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C. We uncovered potential regulatory drivers of CD177+ neutrophil hyperactivation and pathogenicity that may be targeted as a single therapeutic strategy for either KD or MIS-C.

Multimode Luminescence with Temperature and Energy Level Synergistic Dependence in Rare Earth Halide DPs for Advanced Multifunctional Applications.

Rare-earth halide double perovskites (DPs) have attracted extensive attention due to their excellent optoelectronic performance. However, the correlation between luminescence performance, crystal structure, and temperature, as well as the inherent energy transfer mechanism, is not well understood. Herein, Lanthanide ions (Ln3+: Nd3+ or Dy3+) as the co-dopants are incorporated into Sb3+ doped Cs2NaYbCl6 DPs to construct energy transfer (ET) models to reveal the effects of temperature and energy levels of rare earth on luminescence and ET. The different excited state structures of Sb3+-Ln3+ doped Cs2NaYbCl6 DPs at different temperatures and relative positions of energy levels of rare earth synergistically determine the physical processes of luminescence. These multi-mode luminescent materials exhibit good performance in anti-counterfeiting, NIR imaging, and temperature sensing. This work provides new physical insights into the effects of temperature and energy levels of rare earth on the energy transfer mechanism and related photophysical process.

Excited State Regulated Emission in Hybrid Indium Halides via Crystal Structure Switch.

Organic-inorganic metal halides have become one of the most promising materials in the next generation of optoelectronic applications due to their high charge carrier mobility and tunable band gaps. In this study, Sb:PA6InCl9 and Sb:PA4NaInCl8 single crystals were prepared through evaporation crystallization, respectively. Due to the different degrees of lattice distortions, the highly efficient yellow emission in Sb:PA6InCl9 at 610 nm and the green emission in Sb:PA4NaInCl8 at 545 nm were achieved by regulation of the excited state, respectively. By introducing additional sodium ions in the post-treatment, we found that the zero-dimensional Sb:PA6InCl9 could rapidly convert into a two-dimensional layered structure of Sb:PA4NaInCl8, thus resulting in a novel green/yellow emission switch. This work guides the structural and performance control of organic-inorganic hybrid In-based metal halides and offers broad prospects for luminescent switching in anticounterfeiting applications.

[Prevalence and risk factors of hyperuricemia among freshmen at Beijing Sport University from 2021 to 2022].

OBJECTIVE: To investigate the prevalence of hyperuricemia among freshmen enrolled in Beijing Sport University and to explore the influencing factors of hyperuricemia in the college population. METHODS: The study period was from September 2021 to February 2022.3372 freshmen of the class of 2021 from Beijing Sport University in Beijing were selected as the study subjects, and two blood uric acid tests were performed on non-same days to calculate the prevalence of the population and to explore the risk factors of hyperuricemia in the college student population using a case-control method.246 people were selected from the hyperuricemia patients of the population to be included in the case group by convenience sampling, and 211 people were selected from the non-hyperuricemia persons of the population to be included in the control group. They were included in the control group, underwent physical and laboratory examinations, and were retrospectively surveyed with questionnaires that included general information such as age, gender, specialty, place of birth, and diet related to hyperuricemia, awareness of hyperuricemia disease, physical activity level, and sleep. Statistical analysis was performed using chi-square analysis, one-way Logistic regression analysis, and multi-factor logistic regression analysis. RESULTS: The number of patients actually diagnosed with hyperuricemia by two blood uric acid tests on non-same days was 479, with a population prevalence rate of 14.21%. Among them, the number of males in the diseased population was 391(22.39%), and the number of females in the diseased population was 88(5.41%). A total of 457 subjects were enrolled in the case-control study, among them, 246 in the case group(218 males and 28 females, average age 19.74 years), 211 in the control group(177 males and 34 females, average age 19.93 years), and 247 in the case group, 211 in the control group, and 2 groups of subjects were included. A total of 211 subjects, and there was no significant difference between the 2 groups in terms of gender composition and age distribution. One-way logistic regression analysis showed that central obesity(OR=31.52, 95%CI 7.59-130.86), obesity(OR=2.59, 95%CI 1.20-5.58), overweight(OR=1.67, 95%CI 1.08-2.59), frequent consumption of fresh vegetables(OR=0.66, 95%CI 0.43-0.99), and drinking 1500-2000 mL of water per day(OR=0.63, 95%CI 0.41-0.95) were associated with hyperuricemia, and multifactorial Logistic regression analyses were performed to analyze the above factors, and finally central obesity(OR=32.05, 95%CI 7.65-134.20), BMI obesity(OR=3.22, 95%CI 1.44-7.20), and daily water intake of 1500-2000 mL(OR=0.60, 95%CI 0.37-0.95) were included in the model at the level of P=0.05. CONCLUSION: The current high prevalence of hyperuricemia in the college student population, which is more prevalent in male college students. Obesity and central obesity are risk factors for hyperuricemia in young college students, and daily water intake of 1500-2000 mL is a protective factor.

Diagnostic Potential of Plasma Extracellular Vesicle miR-483-3p and Let-7d-3p for Sepsis.

Background: microRNAs (miRNAs) from circulating extracellular vesicles (EVs) have been reported as disease biomarkers. This study aimed to identify the diagnostic value of plasma EV-miRNAs in sepsis. Methods: EVs were separated from the plasma of sepsis patients at admission and healthy controls. The expression of EV-miRNAs was evaluated by microarray and qRT-PCR. Results: A preliminary miRNA microarray of plasma EVs from a discovery cohort of 3 sepsis patients at admission and three healthy controls identified 11 miRNAs with over 2-fold upregulation in sepsis group. Based on this finding, EV samples from a validation cohort of 37 sepsis patients at admission and 25 healthy controls were evaluated for the expression of the 6 miRNAs relating injury and inflammation via qRT-PCR. Elevated expression of miR-483-3p and let-7d-3p was validated in sepsis patients and corroborated in a mouse model of sepsis. miR-483-3p and let-7d-3p levels positively correlated with the disease severity. Additionally, a combination of miR-483-3p and let-7d-3p had diagnostic value for sepsis. Furthermore, bioinformatic analysis and experimental validation showed that miR-483-3p and let-7d-3p target pathways regulating immune response and endothelial function. Conclusion: The present study reveals the potential role of plasma EV-miRNAs in the pathogenesis of sepsis and the utility of combining miR-483-3p and let-7d-3p as biomarkers for early sepsis diagnosis.

Single-cell profiling reveals novel cellular heterogeneity of monocytes during Hymenoptera venom allergy.

Background: Hymenoptera stings can induce dysregulated inflammation and immediate hypersensitivity reactions including anaphylaxis. However, the molecular mechanisms underlying peripheral immune responses during Hymenoptera venom allergy (HVA) remain elusive. Methods: Here we determined the single-cell transcriptomic profiling from highly heterogeneous peripheral blood cells in patients with HVA through unbiased single-cell RNA sequencing and multiple models of computational analyses. Results: Through clustering analysis by uniform manifold approximation and projection, we revealed an increased number of monocytes in the acute phase and identified innate immune responses, leukocyte activation, and cellular detoxification as the main involved biological processes. We used filter analysis to identify that CLU that encodes clusterin was highly expressed in monocytes, and the co-expressed genes of CLU further supported the key role of monocyte. We further used pseudo-temporal ordering of cells and scRNA velocity analysis to delineate disease-associated monocyte lineages and states in patients with HVA. Conclusions: Our comprehensive molecular profiling of blood samples from patients with HVA revealed previously unknown molecular changes, providing important insights into the mechanism of venom allergy and potential therapeutic targets.

CCDC167 as a potential therapeutic target and regulator of cell cycle-related networks in breast cancer.

According to cancer statistics reported in 2020, breast cancer constitutes 30% of new cancer cases diagnosed in American women. Histological markers of breast cancer are expressions of the estrogen receptor (ER), the progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2. Up to 80% of breast cancers are grouped as ER-positive, which implies a crucial role for estrogen in breast cancer development. Therefore, identifying potential therapeutic targets and investigating their downstream pathways and networks are extremely important for drug development in these patients. Through high-throughput technology and bioinformatics screening, we revealed that coiled-coil domain-containing protein 167 (CCDC167) was upregulated in different types of tumors; however, the role of CCDC167 in the development of breast cancer still remains unclear. Integrating many kinds of databases including ONCOMINE, MetaCore, IPA, and Kaplan-Meier Plotter, we found that high expression levels of CCDC167 predicted poor prognoses of breast cancer patients. Knockdown of CCDC167 attenuated aggressive breast cancer growth and proliferation. We also demonstrated that treatment with fluorouracil, carboplatin, paclitaxel, and doxorubicin resulted in decreased expression of CCDC167 and suppressed growth of MCF-7 cells. Collectively, these findings suggest that CCDC167 has high potential as a therapeutic target for breast cancer.