No causal relationship between serum urate and neurodegenerative diseases: A Mendelian randomization study.

OBJECTIVE: Observational studies have shown that increased serum urate is associated with a lower risk of neurodegenerative diseases (NDs), but the causality remains unclear. We employed a two-sample Mendelian randomization (MR) approach to assess the causal relationship between serum urate and four common subtypes of NDs, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). METHODS: Serum urate data came from the CKDGen Consortium. GWAS data for PD, AD, ALS, and MS were obtained from four databases in the primary analysis and then acquired statistics from the FinnGen consortium for replication and meta-analysis. Inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods were applied in the MR analyses. Pleiotropic effects, heterogeneity, and leave-one-out analyses were evaluated to validate the results. RESULTS: There was no evidence for the effect of serum urate on PD (OR: 1.00, 95 % CI: 0.90-1.11, P = 0.97), AD (OR: 1.02, 95 % CI: 1.00-1.04, P = 0.06), ALS (OR: 1.05, 95 % CI: 0.97-1.13, P = 0.22), and MS (OR: 1.01, 95 % CI: 0.89-1.14, P = 0.90) risk when combined with the FinnGen consortium, neither was any evidence of pleiotropy detected between the instrumental variables (IVs). CONCLUSION: The MR analysis suggested that serum urate may not be causally associated with a risk of PD, AD, ALS, and MS.

The Impact of a Multidisciplinary Experiential Training Model on Knowledge, Attitude and Practice of Healthcare Workers in Maternity Health Management: A Preliminary Study.

Background: Maternity health management has always been the area of concern and considering, and considering its complexity and multidisciplinary, it is necessary to provide effective training for healthcare workers. Purpose: To evaluate the impact of a multidisciplinary experiential training model on the knowledge, attitude, and practice of healthcare workers in maternity health management. Patients and Methods: We conducted a novel educational model, Multidisciplinary Maternity Health Experiential Training based on Knowledge, Attitude and Practice (MMHET), which combined theoretical knowledge, practical skills, and human-centred humanistic care, offering a comprehensive offline education program supported by online teaching materials structured around knowledge graphs. Pre- and post-test surveys were used to assess the changes in participants' knowledge, attitudes, and practices. Results: From May to July 2023, a total of 322 participants attended the course, and only a small percentage had participated in experiential training. For all topics, the vast majority of participants endorsed the course, and the attitude content had the highest percentage of participants who said they agreed. Among the groups with different years of working life, the highest percentage of participants in the >20 years group strongly endorsed the course. Conclusion: The preliminary findings indicate that the MMHET model is well-received and feasible, demonstrating its potential to enhance maternity health management education.

Simulation Study on Temperature Control Performance of Lithium-Ion Battery Fires by Fine Water Mist in Energy Storage Stations.

The combustion of lithium-ion batteries is characterized by fast ignition, prolonged duration, high combustion temperature, release of significant energy, and generation of a large number of toxic gases. Fine water mist has characteristics such as a high fire extinguishing efficiency and environmental friendliness. In order to thoroughly investigate the temperature control effect of fine water mist on lithium-ion battery fires. This study employs numerical simulation methods, utilizing PyroSim software to simulate the fire process in lithium-ion battery energy storage compartments. First, we focus on the variation patterns of flame, changes in combustion temperature, and heat release rate over time at environmental temperatures of 10, 25, and 35 °C. Subsequently, the suppression of flame, reduction in temperature, and changes in heat release rate are simulated for water mist in lithium-ion battery fires. The simulation results indicate that the environmental temperature has a considerable impact on the flame but a lesser effect on the heat release rate. Fine water mist effectively impedes the spread of thermal runaway between internal battery core cells, leading to a reduction in the flame size and a significant decrease in the maximum temperature and heat release rate. The numerical simulation results can provide scientific guidance for the prevention and control of fires in lithium-ion battery energy storage compartments.

Two new saponins from the rhizomes of Paris yunnanensis Franch.

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

A Biodegradable, Stretchable, Healable, and Self-Powered Optoelectronic Synapse Based on Ionic Gelatins for Neuromorphic Vision System.

Optoelectronic synapses have gained increasing attentions as a fundamental building block in the development of neuromorphic visual systems. However, it remains a challenge to integrate multiple functions into a single optoelectronic synapse that can be widely applied in wearable artificial intelligence and implantable neuromorphic vision systems. In this study, a stretchable optoelectronic synapse based on biodegradable ionic gelatin heterojunction is successfully developed. This device exhibits self-powered synaptic plasticity behavior with broad spectral response and excellent elastic properties, yet it degrades rapidly upon disposal. After complete cleavage, the device can be fully repaired within 1 min, which is mainly attributed to the non-covalent interactions between different molecular chains. Moreover, the recovery and reprocessing of the ionic gelatins result in optoelectronic properties that are virtually indistinguishable from their original state, showcasing the resilience and durability of ionic gelatins. The combination of biodegradability, stretchability, self-healing, zero-power consumption, ease of large-scale preparation, and low cost makes the work a major step forward in the development of biodegradable and stretchable optoelectronic synapses.

Simultaneous detection of 5-methylcytosine and 5-hydroxymethylcytosine at specific genomic loci by engineered deaminase-assisted sequencing.

Cytosine modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), play crucial roles in numerous biological processes. Current analytical methods are often constrained to the separate detection of either 5mC or 5hmC, or the combination of both modifications. The ability to simultaneously detect C, 5mC, and 5hmC at the same genomic locations with precise stoichiometry is highly desirable. Herein, we introduce a method termed engineered deaminase-assisted sequencing (EDA-seq) for the simultaneous quantification of C, 5mC, and 5hmC at the same genomic sites. EDA-seq utilizes a specially engineered protein, derived from human APOBEC3A (A3A), known as eA3A-M5. eA3A-M5 exhibits distinct deamination capabilities for C, 5mC, and 5hmC. In EDA-seq, C undergoes complete deamination and is sequenced as T. 5mC is partially deaminated resulting in a mixed readout of T and C, and 5hmC remains undeaminated and is read as C. Consequently, the proportion of T readouts (P T) reflects the collective occurrences of C and 5mC, regulated by the deamination rate of 5mC (R 5mC). By determining R 5mC and P T values, we can deduce the precise levels of C, 5mC, and 5hmC at particular genomic locations. We successfully used EDA-seq to simultaneously measure C, 5mC, and 5hmC at specific loci within human lung cancer tissue and their normal counterpart. The results from EDA-seq demonstrated a strong concordance with those obtained from the combined application of BS-seq and ACE-seq methods. EDA-seq eliminates the need for bisulfite treatment, DNA oxidation or glycosylation and uniquely enables simultaneous quantification of C, 5mC and 5hmC at the same genomic locations.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

Identification of core genes shared by ischemic stroke and myocardial infarction using an integrated approach.

BACKGROUND: Both ischemic stroke (IS) and myocardial infarction (MI) are caused by vascular occlusion that results in ischemia. While there may be similarities in their mechanisms, the potential relationship between these 2 diseases has not been comprehensively analyzed. Therefore, this study explored the commonalities in the pathogenesis of IS and MI. METHODS: Datasets for IS (GSE58294, GSE16561) and MI (GSE60993, GSE61144) were downloaded from the Gene Expression Omnibus database. Transcriptome data from each of the 4 datasets were analyzed using bioinformatics, and the differentially expressed genes (DEGs) shared between IS and MI were identified and subsequently visualized using a Venn diagram. A protein-protein interaction (PPI) network was constructed using the Interacting Gene Retrieval Tool database, and identification of key core genes was performed using CytoHubba. Gene Ontology (GO) term annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the shared DEGs were conducted using prediction and network analysis methods, and the functions of the hub genes were determined using Metascape. RESULTS: The analysis revealed 116 and 1321 DEGs in the IS and MI datasets, respectively. Of the 75 DEGs shared between IS and MI, 56 were upregulated and 19 were downregulated. Furthermore, 15 core genes - S100a12, Hp, Clec4d, Cd163, Mmp9, Ormdl3, Il2rb, Orm1, Irak3, Tlr5, Lrg1, Clec4e, Clec5a, Mcemp1, and Ly96 - were identified. GO enrichment analysis of the DEGs showed that they were mainly involved in the biological functions of neutrophil degranulation, neutrophil activation during immune response, and cytokine secretion. KEGG analysis showed enrichment in pathways pertaining to Salmonella infection, Legionellosis, and inflammatory bowel disease. Finally, the core gene-transcription factor, gene-microRNA, and small-molecule relationships were predicted. CONCLUSION: These core genes may provide a novel theoretical basis for the diagnosis and treatment of IS and MI.

Effects of Mindfulness and Life-Skills Training on Emotion Regulation and Anxiety Symptoms in Chinese Migrant Children: A Randomized Controlled Trial.

PURPOSE: China's rapid urbanization has been associated with increased mental health challenges, especially in rural-to-urban migrant children. This study evaluates the effects of mindfulness and life-skills (LS) training on emotional regulation and anxiety symptoms from a randomized controlled trial aimed at improving the mental health of Chinese migrant children. METHODS: Two intervention arms-mindfulness training (MT) and MT plus LS mentorship (MT + LS)-were compared to a waitlist control group of 368 migrant children aged 9-17 years. Volunteers were trained to deliver interventions to 285 migrant children in small groups of 15 for eight weeks weekly. Social integration varied: migrant children mixed with local children at public schools were considered highly integrated, those in migrant-only classrooms at public schools had intermediate levels of integration, and children in private migrant schools had low integration. Emotion regulation and anxiety symptoms were assessed preintervention, postintervention, and three months postintervention. RESULTS: Postintervention and compared to the control group, children with high social integration in the MT arm showed increased cognitive reappraisal ability (p < .05) but higher physical anxiety (p < .01). Children with high social integration in the MT + LS arm had lower anxiety symptoms of harm avoidance (p < .01) and physical anxiety (p < .05). Children with low social integration in the MT + LS arm showed lower cognitive reappraisal (p < .01) and poorer overall emotion regulation abilities (p < .01). Three months later, children with intermediate integration in the MT + LS arm had lower separation anxiety (p < .05) and harm avoidance anxiety (p < .05). No other groups showed significant improvements in emotion regulation or reducing in anxiety symptoms three months postintervention. DISCUSSION: Mindfulness and LS training may benefit Chinese migrant children who have higher levels of social integration but increase anxiety in those with lower social integration. Future research should consider the sociocultural context in which a treatment is implemented.

Systematic analysis of the expression profiles and prognostic significance of the MED gene family in renal clear cell carcinoma.

The mediator complex (MED) family is a contributing factor in the regulation of transcription and proliferation of cells, and is closely associated with the development of various types of cancer. However, the significance of the expression levels and prognostic value of MED genes in kidney renal clear cell carcinoma (KIRC) have rarely been reported. The present study analyzed the expression and prognostic potential of MED genes in KIRC. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network (PPI), the Assistant for Clinical Bioinformatics database was used to perform correlation analysis, GEPIA 2 was utilized to draw the Kaplan-Meier plot and analyze prognostic significance and the Tumor Immune Estimation Resource was used to assess the association of MED genes with the infiltration of immune cells in patients with KIRC. A total of 30 MED genes were identified, and among these genes, 11 were selected for the creation of a prognostic gene signature based on the results of a LASSO Cox regression analysis. Furthermore, according to univariate and multivariate analyses, MED7, MED16, MED21, MED25 and MED29 may be valuable independent predictive biomarkers for the prognosis of individuals with KIRC. Furthermore, there were significant differences in the expression levels of MED7, MED21 and MED25 in KIRC among different tumor grades. Additionally, patients with KIRC with high transcription levels of MED7, MED21 and MED29 had considerably longer overall survival times. The expression levels of MED genes were also linked to the infiltration of several immune cells. Overall, MED genes may have potential significance in predicting the prognosis of patients with KIRC.

Prevalence and molecular characteristics of intestinal pathogenic Escherichia coli isolated from diarrheal pigs in Southern China.

Intestinal pathogenic Escherichia coli (InPEC) is one of the most common causes of bacterial diarrhea in farm animals, including profuse neonatal diarrhea and post weaning diarrhea (PWD) in piglets. In this study, we investigated the prevalence of InPEC and associated primary virulence factors among 543 non-duplicate E. coli isolates from diarrheal pigs from 15 swine farms in southern China. Six major virulence genes associated with InPEC were identified among 69 (12.71 %) E. coli isolates and included est (6.62 %), K88 (4.79 %), elt (3.68 %), eae (1.47 %), stx2 (0.92 %) and F18 (0.55 %). Three pathotypes of InPEC were identified including ETEC (8.10 %), EPEC (1.29 %) and STEC/ETEC (0.92 %). In particular, K88 was only found in ETEC from breeding farms, whereas F18 was only present in STEC/ETEC hybrid from finishing farms. Whole genome sequence analysis of 37 E. coli isolates revealed that InPEC strains frequently co-carried multiple antibiotic resistance gene (ARG). est, elt and F18 were also found to co-locate with ARGs on a single IncFIB/IncFII plasmid. InPEC isolates from different pathotypes also possessed different profiles of virulence genes and antimicrobial resistance genes. Population structure analysis demonstrated that InPEC isolates from different pathotypes were highly heterogeneous whereas those of the same pathotype were extremely similar. Plasmid analysis revealed that K88 and/or est/elt were found on pGX18-2-like/pGX203-2-like and pGX203-1-like IncFII plasmids, while F18 and elt/est, as well as diverse ARGs were found to co-locate on IncFII/IncFIB plasmids with a non-typical backbone. Moreover, these key virulence genes were flanked by or adjacent to IS elements. Our findings indicated that both clonal expansion and horizontal spread of epidemic IncFII plasmids contributed to the prevalence of InPEC and the specific virulence genes (F4, F18, elt and est) in the tested swine farms.

Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data.

BACKGROUND: Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. METHODS: Utilizing patient data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. RESULTS: The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. CONCLUSIONS: The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

The Diagnostic Value of Conventional MRI Combined With Diffusion-Weighted Imaging in Microprolactinomas.

BACKGROUND: Turbo spin-echo (TSE) diffusion-weighted imaging (DWI) sequences may reduce susceptibility artifacts and image distortion in sellar region, allowing better visualization of small pituitary lesions, and may be used to assist in the diagnosis of pituitary microadenomas. PURPOSE: To explore the application value of conventional MRI combined with DWI sequences in the diagnosis of microprolactinomas. STUDY TYPE: Prospective. POPULATION: Thirty-four patients in microprolactinomas with high signal on T2WI (HT2-PRL) group (34 females, 34 ± 7 years), 26 patients in microprolactinomas with equal or low signal on T2WI (ELT2-PRL) group (21 females, 34 ± 7 years), 35 patients with hyperprolactinemia (33 females, 32 ± 8 years), and 30 normal controls (25 females, 31 ± 7 years). FIELD STRENGTH/SEQUENCE: TSE sequence at 3 T. ASSESSMENT: Pituitary morphological parameters (such as length and volume), dynamic contrast-enhanced parameters (such as time to peak) and the apparent diffusion coefficients (ADCs) were measured in each group. STATISTICAL TESTS: ANOVA and Mann-Whitney U test were used to compare parameters among groups. Spearman's coefficient was used to evaluate the correlation between variables. ROC analysis was used to assess the performance of the parameters. A P-value <0.05 was considered statistically significant. RESULTS: The pituitary volume of patients in HT2-PRL, ELT2-PRL, and hyperprolactinemia group were 831.00 (747.60, 887.60), 923.63 ± 219.34, and 737.20 (606.40, 836.80) mm3. The pituitary maximum height in these three groups were 7.03 (6.43, 8.63), 8.03 ± 1.41, and 6.63 ± 1.28 mm, respectively. The lesion ADC value was significantly correlated with T2 relative signal intensity (the ratio of signal intensity of microprolactinoma or anterior pituitary to left temporal cortex) (r = 0.821). Compared with patients with hyperprolactinemia, the diagnostic efficacy of T2 relative signal intensity was higher in HT2-PRL group, with an AUC of 0.954, whereas the ADC value was the highest in ELT2-PRL group, with an AUC of 0.924. CONCLUSION: DWI sequences can be used to assist in the diagnosis of pituitary microadenomas. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Neurotoxicity of hexaconazole on rat brain: The aspect of biological rhythm.

Hexaconazole is a widely used and frequently detected fungicide which is also reported to be persistent in environment. The toxicity of Hex to non-organisms such as reproductive toxicity, endocrine disrupting toxicity, and carcinogenic toxicity had been reported. However, study on the Hex-induced neurotoxicity is rare and the mechanism is still unclear. Therefore, in this study, environmental related concentrations of Hex were chosen to investigate the effects of Hex on nervous system from the aspect of biological rhythm under 90 d sub-chronic exposure. The results showed that Hex significantly affected the cognitive function of rats resulting in the deterioration of learning and memory ability and induced oxidative stress in rat brain. Moreover, the notable changes of neurotransmitters in rat brain suggested the disorder of nerve signaling conduction induced by Hex. The influence of Hex on biological rhythm was further detected which showed that levels of rhythm regulatory genes and proteins significantly disturbed at four monitored time periods. Based on these results, it was supposed that the underlying mechanism of Hex-induced cognitive dysfunction might through oxidative stress pathway. Our findings could systematically and comprehensively clarify the effects of Hex on nervous system and were helpful for prevention neurological diseases induced by triazole pesticides.

Development and validation of a HPLC method for the determination of chemical and radiochemical purity of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET)), a PET radiotracer for the imaging of brain tumor.

A novel HPLC method was developed and validated to determine radiochemical identity, radiochemical purity and chemical purity for the analysis of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET). In this method, an analytical Phenomenex Gemini C18 column was used with an isocratic eluent of 7 % ethanol and 93 % 50 mM potassium phosphate buffer (pH = 6.9). The flow rate was 1.0 mL/min and the injection volume was 10 µL. A photo-diode array detector set at 220 nm was used for UV mass detection and a single channel, high sensitivity radiation detector was used. The method validation assays including specificity, linearity, precision, accuracy, and robustness were evaluated. Results show that the method was suitable for qualitative and quantitative determination of radiochemical and chemical purity of [18F]FET. This system has been routinely used for the analysis of more than 120 batches of [18F]FET with radiochemical yield 23.7 ± 6 % (no decay corrected) and molar activity 593 ± 284 GBq/µmole in our facility to support human use.

Higher systemic inflammation response index is associated with increased risk of heart failure in adults: An observational study.

Inflammation has been established to play a crucial role in the onset of heart failure (HF) for many years, and the systemic inflammation response index (SIRI) is a new and comprehensive indicator reflecting the inflammation status in human body. The aim of this investigation was to determine the potential relationship between HF and SIRI in adults. For this investigation, we used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2009 to 2018. The study utilized multivariable linear regression models to examine the potential independent relationship between HF and SIRI. Additionally, a subgroup analysis and interaction test were carried out. To illustrate the nonlinear relationship, threshold effect analysis and fitted smoothing curves were also used. 26,303 eligible subjects aged ≥ 20 years were enrolled as the final samples. HF participants exhibited significant higher SIRI compared with non-HF participants [1.89 ±â€…1.33 vs 1.25 ±â€…0.95 (1000 cells/µL), P < .0001]. Multivariate logistic regression showed that those in the highest SIRI quartile had a significantly greater risk of HF by 130% (OR = 2.30, 95% CI 1.41-3.76; P < .0001). In addition, nonlinear relationship between HF and SIRI with the inflection point of 2.2 (1000 cells/µL) was observed. According to our research, adult HF prevalence and SIRI are positively correlated. This implies that SIRI could be a valuable biomarker for determining HF risk in the clinic.

A micropeptide TREMP encoded by lincR-PPP2R5C promotes Th2 cell differentiation by interacting with PYCR1 in allergic airway inflammation.

BACKGROUND: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. METHODS: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. RESULTS: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP-/- CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP-/- mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP-/- mice and PYCR1-/- mice. Similar to TREMP-/- mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1-/- mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. CONCLUSIONS: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.