Predicting protein functions using positive-unlabeled ranking with ontology-based priors.

Automated protein function prediction is a crucial and widely studied problem in bioinformatics. Computationally, protein function is a multilabel classification problem where only positive samples are defined and there is a large number of unlabeled annotations. Most existing methods rely on the assumption that the unlabeled set of protein function annotations are negatives, inducing the false negative issue, where potential positive samples are trained as negatives. We introduce a novel approach named PU-GO, wherein we address function prediction as a positive-unlabeled ranking problem. We apply empirical risk minimization, i.e. we minimize the classification risk of a classifier where class priors are obtained from the Gene Ontology hierarchical structure. We show that our approach is more robust than other state-of-the-art methods on similarity-based and time-based benchmark datasets. AVAILABILITY AND IMPLEMENTATION: Data and code are available at https://github.com/bio-ontology-research-group/PU-GO.

Mendelian randomization and colocalization analysis reveal novel drug targets for myasthenia gravis.

OBJECTIVE: Myasthenia gravis (MG) is a complex autoimmune disease affecting the neuromuscular junction with limited drug options, but the field of MG treatment recently benefits from novel biological agents. We performed a drug-targeted Mendelian randomization (MR) study to identify novel therapeutic targets of MG. METHODS: Cis-expression quantitative loci (cis-eQTL), which proxy expression levels for 2176 druggable genes, were used for MR analysis. Causal relationships between genes and disease, identified by eQTL MR analysis, were verified by comprehensive sensitivity, colocalization, and protein quantitative loci (pQTL) MR analyses. The protein-protein interaction (PPI) analysis was also performed to extend targets, followed by enzyme-linked immunosorbent assay (ELISA) to explore the serum level of drug targets in MG patients. A phenome-wide MR analysis was then performed to assess side effects with a clinical trial review assessing druggability. RESULTS: The eQTL MR analysis has identified eight potential targets for MG, one for early-onset MG and seven for late-onset MG. Further colocalization analyses indicated that CD226, CDC42BPB, PRSS36, and TNFSF12 possess evidence for colocalization with MG or late-onset MG. pQTL MR analyses identified the causal relations of TNFSF12 and CD226 with MG and late-onset MG. Furthermore, PPI analysis has revealed the protein interaction between TNFSF12-TNFSF13(APRIL) and TNFSF12-TNFSF13B(BLyS). Elevated TNFSF13 serum level of MG patients was also identified by ELISA experiments. This study has ultimately proposed three promising therapeutic targets (TNFSF12, TNFSF13, TNFSF13B) of MG. CONCLUSIONS: Three drug targets associated with the BLyS/APRIL pathway have been identified. Multiple biological agents, including telitacicept and belimumab, are promising for MG therapy.

Adenosine 5'monophosphate-activated protein kinase activation reduces the risks of psoriasis and its comorbidities: a mendelian randomisation study in the UK Biobank.

OBJECTIVE: Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank(UKB). METHODS: To avoid immortal-time-biases in pharmacoepidemiologic studies, Mendelian randomisation was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with HbA1c, serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 407 159 participants were analyzed, including 9,126 EOP and 3,324 LOP. The AMPK-genetic-risk-score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022-1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062-1.395) in male psoriasis patients. CONCLUSIONS: AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed.

A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma.

BACKGROUND: The prognosis of wild-type BRAF cutaneous melanoma (WT Bf-CM) patients remains poor due to the lack of therapeutic options. However, few studies have investigated the factors contributing to the prognosis of WT Bf-CM patients. METHODS: In this paper, we proposed and validated a novel 7-RNA based signature to predict the prognosis of WT Bf-CM by analyzing the information from TCGA database. RESULTS: Dependence of this signature to other clinical factors were verified and a nomogram was also drawn to promote its application in clinical practice. Functional analysis suggested that the predictive function of this signature might attribute to the prediction of the up-regulation of RNA splicing, transcription, and cellular proliferation in the high-risk group, which have been demonstrated to be linked to malignancy of cancer. Moreover, functional analysis and therapy response analysis supported that the prognosis is highly related to PI3K/Akt/mTOR pathway among WT Bf-CM patients. CONCLUSION: Collectively, this study will provide a preliminary bioinformatics evidence for the molecular mechanism and potential drug targets that could improving WT Bf-CM prognosis.

Integrative transcriptomic, proteomic, and machine learning approach to identifying feature genes of atrial fibrillation using atrial samples from patients with valvular heart disease.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia with poorly understood mechanisms. We aimed to investigate the biological mechanism of AF and to discover feature genes by analyzing multi-omics data and by applying a machine learning approach. METHODS: At the transcriptomic level, four microarray datasets (GSE41177, GSE79768, GSE115574, GSE14975) were downloaded from the Gene Expression Omnibus database, which included 130 available atrial samples from AF and sinus rhythm (SR) patients with valvular heart disease. Microarray meta-analysis was adopted to identified differentially expressed genes (DEGs). At the proteomic level, a qualitative and quantitative analysis of proteomics in the left atrial appendage of 18 patients (9 with AF and 9 with SR) who underwent cardiac valvular surgery was conducted. The machine learning correlation-based feature selection (CFS) method was introduced to selected feature genes of AF using the training set of 130 samples involved in the microarray meta-analysis. The Naive Bayes (NB) based classifier constructed using training set was evaluated on an independent validation test set GSE2240. RESULTS: 863 DEGs with FDR < 0.05 and 482 differentially expressed proteins (DEPs) with FDR < 0.1 and fold change > 1.2 were obtained from the transcriptomic and proteomic study, respectively. The DEGs and DEPs were then analyzed together which identified 30 biomarkers with consistent trends. Further, 10 features, including 8 upregulated genes (CD44, CHGB, FHL2, GGT5, IGFBP2, NRAP, SEPTIN6, YWHAQ) and 2 downregulated genes (TNNI1, TRDN) were selected from the 30 biomarkers through machine learning CFS method using training set. The NB based classifier constructed using the training set accurately and reliably classify AF from SR samples in the validation test set with a precision of 87.5% and AUC of 0.995. CONCLUSION: Taken together, our present work might provide novel insights into the molecular mechanism and provide some promising diagnostic and therapeutic targets of AF.

Role of purines in regulation of metabolic reprogramming.

Purines, among most influential molecules, are reported to have essential biological function by regulating various cell types. A large number of studies have led to the discovery of many biological functions of the purine nucleotides such as ATP, ADP, and adenosine, as signaling molecules that engage G protein-coupled or ligand-gated ion channel receptors. The role of purines in the regulation of cellular functions at the gene or protein level has been well documented. With the advances in multiomics, including those from metabolomic and bioinformatic analyses, metabolic reprogramming was identified as a key mechanism involved in the regulation of cellular function under physiological or pathological conditions. Recent studies suggest that purines or purine-derived products contribute to important regulatory functions in many fundamental biological and pathological processes related to metabolic reprogramming. Therefore, this review summarizes the role and potential mechanism of purines in the regulation of metabolic reprogramming. In particular, the molecular mechanisms of extracellular purine- and intracellular purine-mediated metabolic regulation in various cells during disease development are discussed. In summary, our review provides an extensive resource for studying the regulatory role of purines in metabolic reprogramming and sheds light on the utilization of the corresponding peptides or proteins for disease diagnosis and therapy.

Colorimetric determination of the activity of alkaline phosphatase based on the use of Cu(II)-modulated G-quadruplex-based DNAzymes.

A colorimetric detection scheme is introduced for the determination of alkaline phosphatase (ALP) activity based on Cu(II)-modulated G-quadruplex-based DNAzymes. It is exploiting the strong affinity of Cu(II) for pyrophosphate (PPi) upon which the cofactor PPi is trapped by Cu(II). Hence, the activity of the DNAzyme is inhibited. ALP catalyzes the hydrolysis of PPi, causing the release of Cu(II). DNAzyme, in turn, is activated and catalyzes the cleavage of the DNA probe substrate. The released G-rich sequence folds into the G-quadruplex, which can bind hemin and catalyze the oxidation of 2,2'-azinobis (3-ethylbenzothiozoline)-6-sulfonate (ABTS), and this leads to an increase in absorbance at 420 nm. Absorbance increases linearly with increasing ALP activity in 0.07 to 300 U.L-1 range, with a 70 mU.L-1 detection limit. The method was applied in ALP inhibition tests and to the determination of ALP activity in spiked serum samples where it gave satisfactory results. Graphical abstract A colorimetric method has been developed for the detection of alkaline phosphatase based on the use of Cu(II)-modulated G-quadruplex-based DNAzymes.

Progressive Facial Ulcer: A Case Report of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing and painful skin ulcers with distinctive features. As far as we are concerned, there is no previous case report on facial PG in East-Asia. In this case, we describe a case of a 79-year-old man with a 3-month history of progressive painful ulcers on his cheek and upper lip. Initial suspicion of atypical mycobacterium infection led to an ineffective treatment regimen. Comprehensive infectious testing yielded negative results, and a positive pathergy test indicated a potential diagnosis of PG. A skin biopsy confirmed the diagnosis, and the patient showed significant improvement with intravenous methylprednisolone and oral cyclosporine treatment. After three months, complete resolution of the lesions was achieved without recurrence. The case highlights the diagnostic challenges associated with PG, which is often misdiagnosed due to its resemblance to other conditions. Thorough evaluation is crucial to exclude alternative diagnoses, particularly cutaneous infections. Clinical morphology, tissue biopsy, and culture are essential for accurate diagnosis. The presence of pathergy, the development of new lesions following minor trauma, can also be a diagnostic clue.

Allergic Phenotypes and Sarcopenia: Evidence from Observational Studies and Mendelian Randomization Analysis.

Commonly affected in early-life population, the impact of allergic phenotypes on mid- or late-life health is less discussed. This study is to explore the association of allergic phenotypes including atopic dermatitis (AD), asthma, eosinophils count (EC), and sarcopenia. We conducted observational studies and mendelian randomization (MR) analysis based on UK Biobank (UKB), the China Health and Retirement Longitudinal Study (CHARLS) and data from genome-wide association study (GWAS). Based on the UKB data, AD, asthma and EC were positively correlated with pre-sarcopenia and decreased skeletal muscle mass index and hand grip in fully adjusted model. Asthma and EC were significantly associated with sarcopenia while AD was marginally associated (p = 0.095). Based on the CHARLS cohort, asthma significantly added 109.4% risk for pre-sarcopenia in adjusted model (relative risk = 2.094; p = 0.002), respectively. Both asthma (ß = 0.100, p = 0.006) and EC (ß = 0.023, p = 0.017) exerted significantly casual effects on pre-sarcopenia. However, as for sarcopenia, merely EC exhibited a significantly casual effect (ß = 0.005, p = 0.048). Significant casual effects of AD (ß = - 0.027, p = 0.003), asthma (ß = - 0.029, p = 0.027) and EC (ß = - 0.041, p < 0.001) on decreased appendicular lean mass (ALM) were observed using the inverse-variance weighted method and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method. Our results revealed a contributory role of AD, asthma and EC on sarcopenia, especially in terms of decreased ALM, an indicator for sarcopenia diagnosis. The findings of our study will raise the awareness of preventing aging-related disorders or geriatric syndromes among allergic populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00110-4.

Association Between Atopic Dermatitis and Aging: Clinical Observations and Underlying Mechanisms.

As one of the most prevalent chronic inflammatory skin diseases, atopic dermatitis (AD) increasingly affects the aging population. Amid the ongoing global aging trend, it's essential to recognize the intricate relationship between AD and aging. This paper reviews existing knowledge, summarizing clinical observations of associations between AD and aging-related diseases in various systems, including endocrine, cardiovascular, and neurological. Additionally, it discusses major theories explaining the correlation, encompassing skin-mucosal barriers, systemic inflammation and stress, genes, signal transduction, and environmental and behavioral factors. The association between AD and aging holds significant importance, both in population and basic perspectives. While further research is warranted, this paper aims to inspire deeper exploration of inflammation/allergy-aging dynamics and the timely management of elderly patients with AD.

Crossed renal ectopia with rectal cancer: A case report.

BACKGROUND: Crossed renal ectopia (CRE) occurs when one kidney crosses the midline from the primary side to the contralateral side while the ureter remains on the primary side. Rectal cancer, one of the most common malignant tumors of the digestive tract, refers to cancer from the dentate line to the rectosigmoid junction. The concurrent presentation of CRE alongside rectal cancer is an uncommon clinical observation. CASE SUMMARY: Herein, we report a 69-year-old male patient with rectal cancer who was diagnosed with CRE via computed tomography during hospitalization. Following thorough preoperative evaluations, the patient underwent Dixon surgery. CONCLUSION: We performed laparoscopic radical resection of rectal cancer and adequate lymph node removal in a patient with CRE with no postoperative discomfort.

A prediction model identifying glycolysis signature as therapeutic target for psoriasis.

Background: The hyperproliferation featured with upregulated glycolysis is a hallmark of psoriasis. However, molecular difference of keratinocyte glycolysis amongst varied pathologic states in psoriasis remain elusive. Objectives: To characterize glycolysis status of psoriatic skin and assess the potential of glycolysis score for therapeutic decision. Methods: We analyzed 345414 cells collected from different cohorts of single-cell RNA seq database. A new method, Scissor, was used to integrate the phenotypes in GSE11903 to guide single-cell data analysis, allowing identification of responder subpopulations. AUCell algorithm was performed to evaluate the glycolysis status of single cell. Glycolysis signature was used for further ordering in trajectory analysis. The signature model was built with logistic regression analysis and validated using external datasets. Results: Keratinocytes (KCs) expressing SLC2A1 and LDH1 were identified as a novel glycolysis-related subpopulation. Scissor+ cells and Scissor- cells were defined as response and non-response phenotypes. In Scissor+ SLC2A1+ LDH1+ KCs, ATP synthesis pathway was activated, especially, the glycolysis pathway being intriguing. Based on the glycolysis signature, keratinocyte differentiation was decomposed into a three-phase trajectory of normal, non-lesional, and lesional psoriatic cells. The area under the curve (AUC) and Brier score (BS) were used to estimate the performance of the glycolysis signature in distinguishing response and non-response samples in GSE69967 (AUC =0.786, BS =17.7) and GSE85034 (AUC=0.849, BS=11.1). Furthermore, Decision Curve Analysis suggested that the glycolysis score was clinically practicable. Conclusion: We demonstrated a novel glycolysis-related subpopulation of KCs, identified 12-glycolysis signature, and validated its promising predictive efficacy of treatment effectiveness.

Knockdown of lncRNA SNHG16 Attenuates the Proliferation and Radioresistance of Nasopharyngeal Carcinoma Cells by Mediating miR-31-5p/SFN Axis.

Nasopharyngeal carcinoma (NPC) is a rare head and neck tumor that threatens people's health. Radiotherapy is a major treatment for NPC, however, radioresistance of the NPC cells may contribute to treatment failure. LncRNA SNHG16 was upregulated in NPC; however, the function of SNHG16 in radioresistant NPC cells remains unexplored. RT-qPCR was applied for detecting SNHG16, miR-31-5p and SFN levels. MTT assay and colony formation assay were applied to assess the cell viability and proliferation. Dual luciferase was applied for assessing the relation among SNHG16, miR-31-5p and SFN. SFN level in NPC cells was examined by Western blot. The level of SNHG16 and SFN in NPC cells was significantly upregulated by exposure to radiation. In addition, silencing of SNHG16 or miR-31-5p mimics notably attenuated radioresistance of NPC cells. SNHG16 could positively regulate the expression of SFN in NPC cells through binding with miR-31-5p. Furthermore, SNHG16 downregulation obviously attenuated the proliferation and radioresistance of NPC cells by regulation of miR-31-5p/SFN axis. Knockdown of lncRNA SNHG16 attenuates radioresistance of nasopharyngeal carcinoma cells by miR-31-5p/SFN axis. Thus, our research data show a novel method for improving the efficacy of radiotherapy for NPC.

Malignancy in dermatomyositis: a mono-centric retrospective study of 134 patients in China and a potential predictive model.

Objectives: To describe the demographics and phenotypes of malignancies-associated dermatomyositis (MADM) in east China and pinpoint potential factors indicative of malignancies in patients with dermatomyositis and establish a predictive model. Methods: We retrospectively analyzed clinical data from 134 patients with adult-onset dermatomyositis hospitalized between January 2019 and May 2022 in one comprehensive hospital. Clinical data including disease course, initial symptoms and signs, and demographic information were retrieved from the Electronic Medical Records System. Other parameters including myositis-specific autoantibodies profiles, ferritin, sedimentation, etc. were all referable. Multivariable multinomial logistic regression was employed to simulate a model to predict cancer risks. Receiver operating characteristic curve was adopted to evaluate the potency of the model. Results: 134 patients with adult-onset dermatomyositis were aptly enrolled in this study based on inclusive and exclusive criteria: 12 (8.96%) with malignancies, 57 (42.53%) with aberrant tumor biomarkers but no malignancies, 65 (48.51%) with neither malignancies nor abnormal tumor biomarkers. Senior diagnostic age, higher LDH, higher ferritin, positive anti-TIF1γ and anti-Mi2 rather than anti-NXP2 autoantibodies were positive indicators of malignancies. Additionally, neither initial complaints nor signs were found to be correlated to a tendency towards malignancies. Digestive system, nasopharyngeal, and lung malignancies were mostly documented in east China. One multivariable multinomial logistic regression model was established to predict the phenotypes of dermatomyositis on the basis of potential malignancies and the overall sensitivity and specificity was satisfactory. Conclusion: Positivity of anti-TIF1γ and anti-Mi2 autoantibodies are highly indicative of malignancies while the role of anti-NXP2 autoantibody in MADM in the Chinese population remains unclear. The phenotypes of malignancies can be predicted through the model and the predictive power is sufficient. More attention should be paid to malignancies screening in patients with aberrant tumor biomarkers but no malignancies, particularly digestive system, nasopharyngeal, and lung malignancies in patients with dermatomyositis but without malignancies.

Exploring the association and causal effect between white blood cells and psoriasis using large-scale population data.

Introduction: Psoriasis is a chronic inflammatory disease of the skin. A few studies have shown that psoriasis is an immune-mediated disease in which multiple immune cells play crucial roles. However, the association between circulating immune cells and psoriasis remains elusive. Methods: To explore the role of circulating immune cells in psoriasis, 361,322 individuals from the UK Biobank (UKB) and 3,971 patients with psoriasis from China were included to investigate the association between white blood cells and psoriasis via an observational study. Genome-wide association studies (GWAS) and Mendelian randomization (MR) were used to evaluate the causal relationship between circulating leukocytes and psoriasis. Results: The risk of psoriasis increased with high levels of monocytes, neutrophils, and eosinophils (relative risks and 95% confidence intervals, respectively: 1.430 (1.291-1.584) for monocytes, 1.527 (1.379-1.692) for neutrophils, and 1.417 (1.294-1.551) for eosinophils). Upon further MR analysis, eosinophils showed a definite causal relationship with psoriasis (odds ratio of inverse-variance weighted: 1.386, 95% confidence intervals: 1.092-1.759) and a positive correlation with the psoriasis area and severity index (PASI) score (P = 6.6 × 10-5). The roles of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) in psoriasis were also assessed. More than 20,000 genetic variations associated with NLR, PLR, and LMR were discovered in a GWAS analysis using the UKB data. Following adjustment for covariates in the observational study, NLR and PLR were shown to be risk factors for psoriasis, whereas LMR was a protective factor. MR results indicated that there was no causal relationship between these three indicators and psoriasis; however, NLR, PLR, and LMR correlated with the PASI score (NLR: rho = 0.244, P = 2.1 × 10-21; PLR: rho = 0.113, P = 1.4 × 10-5; LMR: rho = -0.242, P = 3.5×10-21). Discussion: Our findings revealed an important association between circulating leukocytes and psoriasis, which is instructive for the clinical practice of psoriasis treatment.

The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients.

Background: JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking. Objective: Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis. Methods: Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata. Results: 6 randomized controlled trials with 1455 patients exhibited SALT50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT5 was 0.71(95% CI, 0.65-0.78), SALT50 was 0.54(95% CI 0.46-0.63), SALT90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions. Limitations: Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data. Conclusion: JAK inhibitors are effective in alopecia areata, although associated with an increased risk.

Auditory and cross-modal attentional bias toward positive natural sounds: Behavioral and ERP evidence.

Recently, researchers have expanded the investigation into attentional biases toward positive stimuli; however, few studies have examined attentional biases toward positive auditory information. In three experiments, the present study employed an emotional spatial cueing task using emotional sounds as cues and auditory stimuli (Experiment 1) or visual stimuli (Experiment 2 and Experiment 3) as targets to explore whether auditory or visual spatial attention could be modulated by positive auditory cues. Experiment 3 also examined the temporal dynamics of cross-modal auditory bias toward positive natural sounds using event-related potentials (ERPs). The behavioral results of the three experiments consistently demonstrated that response times to targets were faster after positive auditory cues than they were after neutral auditory cues in the valid condition, indicating that healthy participants showed a selective auditory attentional bias (Experiment 1) and cross-modal attentional bias (Experiment 2 and Experiment 3) toward positive natural sounds. The results of Experiment 3 showed that N1 amplitudes were more negative after positive sounds than they were after neutral sounds, which further provided electrophysiological evidence that positive auditory information enhances attention at early stages in healthy adults. The results of the experiments performed in the present study suggest that humans exhibit an attentional bias toward positive natural sounds.

Association Between Atopic Dermatitis, Asthma, and Serum Lipids: A UK Biobank Based Observational Study and Mendelian Randomization Analysis.

Background: Both atopic diseases and dysregulation of serum lipids (SLs) add to significant health burden, but evidences about their association are inconsistent. Objective: This work is to evaluate the association between asthma/atopic dermatitis (AD) and SLs and investigate the potential causal relationship. Methods: A large-scale cross-sectional study based on the UK Biobank (UKB) and then examined the casual relationships between SLs with asthma/AD based on a Mendelian randomization (MR) analysis. Results: A total of 502,505 participants were included in analysis. After full adjustment, AD was associated with lower TG (ß = -0.006; 95%CI, -0.010 to -0.002; P = 0.006), lower LDL (ß = -0.004; 95%CI, -0.006 to -0.002, P < 0.001), and lower TC (ß = -0.004; 95%CI, -0.005 to -0.002; P < 0.001) but insignificantly correlated to HDL (P = 0.794). Asthma was also inversely correlated to TG (ß = -0.005; 95%CI, = -0.007 to -0.003; < 0.001), LDL (ß = -0.003; 95%CI, -0.004 to -0.002; P < 0.001), and TC (ß = -0.002; 95%CI, -0.003 to -0.002; P < 0.001), but was positively correlated to HDL (ß = 0.004; 95%CI, 0.003 to 0.005; P < 0.001), respectively. In subsequent MR analysis, both allergic diseases and asthma showed a protective effect on TC. Allergic diseases, asthma, and AD all showed a negative effect on LDL. Conclusion: Collectively, we identify a protective causal effect of allergic diseases on serum lipids, as well as a potentially positive association of HDL with asthma. Owing to the largest sample size and the application of IVs in causal inference, this study will provide a robust evidence for the management of asthma and AD and the prevention of dyslipidemia.

A fluorescent assay for alkaline phosphatase activity based on phosphorylation protection and DNAzyme-assisted amplification.

Alkaline phosphatase is one of the most important tool enzymes and diseases indicator, monitoring ALP activity with convenient, precise, efficient and sensitive methods plays a fundamental role in modern life and healthcare industries. In this study, we described a novel method for ALP analysis based on Pb2+ dependent DNAzyme. By modifying DNAzyme sequence with terminal phosphate group and introducing exonuclease I (exo I), we managed to analyze ALP by utilizing its causal function of DNAzyme probe from exo I mediated degradation and function of triggering the subsequent cleavage of the hairpin reporting probe. Other than one amplificative strategy by DNAzyme mediated cleavage and cycle, this system also involved an exo I mediated degradation to further reduce the background noise. Combining stepwise fluorimetry and electrophoresis, we verified the detective mechanism of this proposed method. Further, after selectivity demonstration, this method achieved a considerable LOD of 0.0017 U L-1 and linear range of 0.0025 U L-1 to 250 U L-1. For potential of practical application, this method also exhibited excellent performances in inhibitor screening and intracellular ALP assay, both with a linear fitting equation. Based on these results, this method should be highly committed for improving ALP analysis in modern life industry.