Association between atherogenic index of plasma and new-onset stroke in individuals with different glucose metabolism status: insights from CHARLS.

BACKGROUND: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. METHODS: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan-Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. RESULTS: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan-Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05-1.71), 1.52 (1.19-1.93), and 1.84 (1.45-2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. CONCLUSIONS: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status.

Proteomic profile of the germinating seeds reveals enhanced seedling growth in Arabidopsis rpp1a mutant.

Ribosomal phosphoprotein P1 (RPP1) is an integral component of the P-protein stalk in the 60S subunit of eukaryotic ribosomes and is required for the efficient elongation of translation. Previously, Arabidopsis RPP1A was revealed to be involved in the regulation of seed size and seed storage protein accumulation. In this work, the seedling growth analysis shows that the knockout mutation of Arabidopsis RPP1A significantly promoted seedling growth, particularly in the shoots. The label-free quantitative proteomic analysis demonstrated that a total of 593 proteins were differentially accumulated between the germinating seeds of the wild-type Col-0 and rpp1a mutant. And these proteins were significantly enriched in the intracellular transport, nitrogen compound transport, protein transport, and organophosphate metabolic process. The abundance of proteins involved in the RNA and protein processing processes, including ncRNA processing and protein folding, were significantly increased in the rpp1a mutant. Mutation in RPP1A highlighted the effects on the ribosome, energy metabolism, and nitrogen metabolism. The abundance of enzymes involved in glycolysis and pyruvate mechanism was decreased in the germinating seeds of the rpp1a mutant. Whereas the processes of amino acid biosynthesis, protein processing in endoplasmic reticulum, and biosynthesis of cofactors were enhanced in the germinating seeds of the rpp1a mutant. Taken together, the lack of RPP1A triggered changes in other ribosomal proteins, and the higher amino acid contents in the seedlings of the rpp1a mutant probably contributed to enhanced biosynthesis, processing, and transport of proteins, resulting in accelerated growth. Our results show the novel role of a P-protein and shed new light on the regulatory mechanism of seedling growth.

Prognostic significance of the CRAFITY score in hepatocellular carcinoma treated with immunotherapy: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the performance of the CRAFITY (CRP and AFP in immunotherapy) score as a prognostic factor in hepatocellular carcinoma (HCC) treated with immunotherapy. METHODS: The PubMed, Cochrane Library, and Web of Science databases were searched for published studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) outcomes were pooled using fixed- and random-effects models. Odds ratios (ORs) with 95% CI were used to measure the association of individual CRAFITY scores with the disease control rate (DCR). RESULTS: Four eligible studies comprising 786 patients were included. The results indicate that a lower CRAFITY score is a significant predictor of better OS (HR = 0.22, 95% CI: 0.10-0.50) and PFS (HR = 0.36, 95% CI: 0.23-0.55) outcomes. In addition, the DCR was significantly higher in patients with lower CRAFITY scores (OR = 3.16, 95% CI: 2.00-4.99). A significant positive association between low CRAFITY scores and favorable prognoses was also observed in Barcelona Clinic Liver Cancer stage B/C/D patients. CONCLUSION: In this study, a low CRAFITY score was associated with better overall outcomes in HCC patients treated with immunotherapy. However, this finding requires further investigation.

Vitamin D status in hospitalized COVID­19 patients is associated with disease severity and IL-5 production.

BACKGROUND: There are many studies on the relationship between vitamin D and coronavirus disease 2019 (COVID-19), while the results are matters of debate and the mechanisms remain unknown. The present study was performed to assess the impact of serum 25-hydroxyvitamin D [25(OH)D] levels on the severity of disease in hospitalized COVID-19 patients and identify potential mechanisms of 25(OH)D alterations. METHODS: A total of 399 hospitalized COVID-19 patients were recruited from three centers between December 19, 2022, and February 1, 2023. Medical history, laboratory examination, and radiologic data were retrospectively collected. The patients were divided into four groups based on disease severity. Serum 25(OH)D levels in the patients were determined by the electrochemiluminescence method and cytokines were detected by flow cytometry. The relationship between serum 25(OH)D status and the severity of COVID-19, and the correlation between 25(OH)D levels and cytokines in COVID-19 patients were assessed. RESULTS: Levels of 25(OH)D were significantly lower in the deceased group than in the other three groups (P < 0.05), and lower in the critical group than in the general group (P < 0.05). There were no significant differences in the 25(OH)D levels between the general and severe groups (P > 0.05). The levels of 25(OH)D (odds ratio = 0.986, 95% confidence interval: 0.973-0.998, P = 0.024) and IL-5 (odds ratio = 1.239, 95% confidence interval: 1.104-1.391, P = 0.04) were independent risk factors for the severity of COVID-19 disease upon admission. Serum 25(OH)D levels were able to predict the mortality of patients with COVID-19, and the predictive value was even higher when combined with IL-5 levels and eosinophil (Eos) count. Circulating 25(OH)D status correlated negatively with the expression of IL-5 (r=-0.262, P < 0.001) and was positively linked with CD8+ T cell counts (r=-0.121, P < 0.05) in patients with COVID-19. CONCLUSIONS: This study found that the serum 25(OH)D status combined with IL-5 levels and Eos counts could be identified as a predictive factor for recognizing the risk of COVID-19 mortality. The serum 25(OH)D status in COVID-19 patients correlated negatively with the expression of IL-5. The potential mechanism for this relationship is worth further exploration.

Costs and Effects of School-Based Licensed Practical Nurses on Elementary Student Attendance and Chronic Absenteeism.

Despite increasing reliance on licensed practical nurses (LPNs) to provide health services in schools, we do not know whether this is a cost-effective prevention strategy against student absenteeism. Therefore, we evaluated the costs and effectiveness of an LPN-based school nursing program for improving attendance and chronic absenteeism at a large, urban school district in the southeastern USA. We first identified a matched set of 46 elementary schools (23 nurse, 23 no-nurse) by using an optimal multilevel matching algorithm based on student- and school-level characteristics. We then conducted a cost-effectiveness analysis on the matched set, using the ingredients method to estimate societal costs and multilevel regression to estimate effects. The results indicated that despite substantial incremental costs of $68,228 per school, the presence of a full-time LPN was associated with at best negligible improvements, and at worst slight disimprovements, in attendance and chronic absenteeism. We recommend a careful review of the theory of change for LPN-based school nursing programs to clarify the specific inputs and activities that are expected to lead to improved student outcomes. Education agencies should develop explicit assignment, training, monitoring, and auditing plans to ensure LPNs are equitably distributed and that their activities are aligned with the theory of change. Education agencies should also explore whether expanded Medicaid billing can reduce their share of the nursing cost burden.

A Novel Thermal Tactile Sensor Based on Micro Thermoelectric Generator for Underwater Flow Direction Perception.

Underwater vehicles can operate independently in the exploitation of marine resources. However, water flow disturbance is one of the challenges underwater vehicles must face. The underwater flow direction sensing method is a feasible way to overcome the challenges but faces difficulties such as integrating the existing sensors with underwater vehicles and high-cost maintenance fees. In this research, an underwater flow direction sensing method based on the thermal tactility of the micro thermoelectric generator (MTEG) is proposed, with the theoretical model established. To verify the model, a flow direction sensing prototype is fabricated to carry out experiments under three typical working conditions. The three typical flow direction conditions are: condition No. 1, in which the flow direction is parallel to the x-axis; condition No. 2, in which the flow direction is at an angle of 45° to the x-axis; and condition No. 3, which is a variable flow direction condition based on condition No. 1 and condition No. 2. According to the experimental data, the variations and orders of the prototype output voltages under three conditions fit the theoretical model, which means the prototype can identify the flow direction of three conditions. Besides, experimental data show that in the flow velocity range of 0~5 m/s and the flow direction variation range of 0~90°, the prototype can accurately identify the flow direction in 0~2 s. The first time utilizing MTEG on underwater flow direction perception, the underwater flow direction sensing method proposed in this research is cheaper and easier to be applied on the underwater vehicles than traditional underwater flow direction sensing methods, which means it has great application prospects in underwater vehicles. Besides, the MTEG can utilize the waste heat of the underwater vehicle battery as the energy source to achieve self-powered work, which greatly enhances its practical value.

TCOF1 upregulation in triple-negative breast cancer promotes stemness and tumour growth and correlates with poor prognosis.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis. By performing multiomic profiling, we recently uncovered super-enhancer heterogeneity between breast cancer subtypes. Our data also revealed TCOF1 as a putative TNBC-specific super-enhancer-regulated gene. TCOF1 plays a critical role in craniofacial development but its function in cancer remains unclear. METHODS: Overall survival and multivariant Cox regression analyses were conducted using the METABRIC data set. The effect of TCOF1 knockout on TNBC growth and stemness was evaluated by in vitro and in vivo assays. RNA-seq and rescue experiments were performed to explore the underlying mechanisms. RESULTS: TCOF1 is frequently upregulated in TNBC and its elevated expression correlates with shorter overall survival. TCOF1 depletion significantly inhibits the growth and stemness of basal-like TNBC, but not of mesenchymal-like cells, highlighting the distinct molecular dependency in different TNBC subgroups. RNA-seq uncovers several stem cell molecules regulated by TCOF1. We further demonstrate that KIT is a downstream effector of TCOF1 in mediating TNBC stemness. TCOF1 expression in TNBC is regulated by the predicted super-enhancer. CONCLUSIONS: TCOF1 depletion potently attenuates the growth and stemness of basal-like TNBC. Expression of TCOF1 may serve as a TNBC prognostic marker and a therapeutic target.

Oleoylethanolamide inhibits glial activation via moudulating PPARα and promotes motor function recovery after brain ischemia.

Glial activation and scar formation impede the neurological function recovery after cerebral ischemia. Oleoylethanolamide (OEA), a bioactive lipid mediator, shows neuroprotection against acute brain ischemia, however, its long-term effect, especially on glial scar formation, has not been characterized. In this research, we investigate the effect of OEA on glial activation and scar formation after cerebral ischemia in vitro and in vivo experiments. Glial scar formation in vitro model was induced by transforming growth factor ß1 (TGF-ß1) in C6 glial cell culture, and experiment model in vivo was induced by middle cerebral artery occlusion (MCAO) in mice. The protein expressions of the markers of glial activation (S100ß, GFAP, or pSmads) and glial scar (neurocan) were detected by Western blot and/or immunofluorescence staining; To evaluate the role of PPARɑ in the effect of OEA on glial activation, the PPARɑ antagonist GW6471 was used. Behavior tests were used to assay the effect of OEA on motor function recovery 14 days after brain ischemia in mice. Our results show that OEA (10-50 µM) concentration-dependently inhibited the upregulation of S100ß, GFAP, pSmads and neurocan induced by TGF-ß1 in C6 glial cells. At the same time, OEA promoted the protein expression and nuclear transportation of PPARɑ in glial cells. PPARα antagonist GW6471 abolished the effect of OEA on glial activation. In addition, we found that delay administration of OEA inhibited the astrocyte activation and promoted the recovery of motor function after brain ischemia in mice. These results indicate that OEA may be developed into a new candidate for attenuating astrocytic scar formation and improving motor function after ischemic stroke.

Activation of peroxisome proliferation-activated receptor-γ inhibits transforming growth factor-ß1-induced airway smooth muscle cell proliferation by suppressing Smad-miR-21 signaling.

The aims of the current study were to examine the signaling mechanisms for transforming growth factor-ß1 (TGF-ß1)-induced rat airway smooth muscle cell (ASMC) proliferation and to determine the effect of activation of peroxisome proliferation-activated receptor-γ (PPAR-γ) on TGF-ß1-induced rat ASMC proliferation and its underlying mechanisms. TGF-ß1 upregulated microRNA 21 (miR-21) expression by activating Smad2/3, and this in turn downregulated forkhead box O1 (FOXO1) mRNA expression. In addition, TGF-ß1-Smad-miR-21 signaling also downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and thus de-repressed the PI3K-Akt pathway. Depletion of PTEN reduced the nuclear FOXO1 protein level without affecting its mRNA level. Inhibition of the PI3K-Akt pathway or proteasome function reversed PTEN knockdown-induced nuclear FOXO1 protein reduction. Our study further showed that loss of FOXO1 increased cyclin D1 expression, leading to rat ASMC proliferation. Preincubation of rat ASMCs with pioglitazone, a PPAR-γ activator, blocked TGF-ß1-induced activation of Smad2/3 and its downstream targets changes of miR-21, PTEN, Akt, FOXO1, and cyclin D1, resulting in the inhibition of rat ASMC proliferation. Our study suggests that the activation of PPAR-γ inhibits rat ASMC proliferation by suppressing Smad-miR-21 signaling and therefore has a potential value in the prevention and treatment of asthma by negatively modulating airway remodeling.

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP.

Sphingosine-1-phosphate (S1P), a bioactive lipid, has been shown to be elevated in the airways of individuals with asthma and modulates the airway smooth muscle cell (ASMC) functions, yet its underlying molecular mechanisms are not completely understood. The aim of the present study is to address this issue. S1P induced yes-associated protein (YAP) dephosphorylation and nuclear localization via the S1PR2/3/Rho-associated protein kinase (ROCK) pathway, and this in turn increased forkhead box M1 (FOXM1) and cyclin D1 expression leading to ASMC proliferation, migration, and contraction. Pretreatment of cells with S1PR2 antagonist JTE013, S1PR3 antagonist CAY10444, or ROCK inhibitor Y27632 blocked S1P-induced alterations of YAP, FOXM1, cyclin D1, and ASMC proliferation, migration, and contraction. In addition, prior silencing of YAP or FOXM1 with siRNA reversed the effect of S1P on ASMC functions. Taken together, our study indicates that S1P stimulates ASMC proliferation, migration, and contraction by binding to S1PR2/3 and modulating ROCK/YAP/FOXM1 axis and suggests that targeting this pathway might have potential value in the management of asthma.

MicroRNA-27a/b mediates endothelin-1-induced PPARγ reduction and proliferation of pulmonary artery smooth muscle cells.

The down-regulation of peroxisome proliferator-activated receptor γ (PPARγ) expression has been found to correlate with the proliferation of pulmonary artery smooth muscle cells (PASMC), pulmonary vascular remodeling and pulmonary hypertension, while the molecular mechanisms underlying PPARγ reduction in PASMC remain largely unclear. The aim of the current study is to address this issue. Endothelin-1 (ET-1) dose- and time-dependently resulted in PPARγ reduction and proliferation of primary cultured rat PASMC, which was accompanied by the activation of nuclear factor-kappaB (NF-κB) and subsequent induction of microRNA-27a/b (miR-27a/b) expression. Chromatin immunoprecipitation assay revealed that NF-κB directly bound to the promoter regions of miR-27a/b. Luciferase reporter assay identified that miR-27a/b directly regulates the expression of PPARγ in PASMC. Further study indicated that the presence of either NF-κB inhibitor pyrrolidinedithiocarbamate or prior silencing miR-27a/b with anti-miRNA oligonucleotides suppressed ET-1-induced PPARγ reduction and proliferation of PASMC, while overexpression of miR-27a/b reduced PPARγ expression and enhanced PASMC proliferation. Taken together, our study demonstrates that ET-1 stimulates miR-27a/b expression by activation of the NF-κB pathway, which in turn results in PPARγ reduction and contributes to ET-1-induced PASMC proliferation.

Activation of AMPK inhibits PDGF-induced pulmonary arterial smooth muscle cells proliferation and its potential mechanisms.

The aims of the present study were to examine signaling mechanisms for PDGF-induced pulmonary arterial smooth muscle cells (PASMC) proliferation and to determine the effect of AMPK activation on PDGF-induced PASMC proliferation and its underlying mechanisms. PDGF activated PI3K/Akt/mTOR signaling pathway, and this in turn up-regulated Skp2 and consequently reduced p27 leading to PASMC proliferation. Prior incubation of PASMC with metformin induced a dramatic AMPK activation and significantly blocked PDGF-induced cell proliferation. PASMC lacking AMPKα2 were resistant to the inhibitory effect of metformin on PDGF-induced cell proliferation. Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction. Our study suggests that the activation of AMPK negatively regulates mTOR activity to suppress PASMC proliferation and therefore has a potential value in the prevention and treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.

Association between thromboxane A2 receptor polymorphisms and asthma risk: A meta-analysis.

OBJECTIVE: To determine whether there is an association between thromboxane A2 receptor (TBXA2R) gene polymorphisms (+924C/T and +795C/T) and asthma risk by conducting a meta-analysis. DATA SOURCES: Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang database were searched (updated May 1, 2015). STUDY SELECTIONS: Articles evaluating the association between TBXA2R gene polymorphisms and asthma risk were selected. RESULTS: A total of 7 studies on +924C/T polymorphism and 6 studies on +795C/T polymorphism were included in this meta-analysis. There was a significant association between TBXA2R +924C/T polymorphism and asthma risk in the recessive model (OR = 1.33, 95% CI = 1.01-1.75, P = 0.045). No significant association between +795C/T polymorphism and asthma risk in the overall population was demonstrated. In subgroup analyzes, significant association was observed in atopic asthma risk in the recessive model (OR = 1.43, 95% CI = 1.01-2.01, P = 0.043), but no significant association was found between TBXA2R +924C/T polymorphism and asthma risk in Asians (OR = 1.14, 95% CI = 0.80-1.63, P = 0.457). TBXA2R +795C/T polymorphism was associated with aspirin-intolerant asthma (AIA) risk when stratified by asthma subphenotype in the allelic model (OR = 1.30, 95% CI = 1.05-1.60, P = 0.014) and dominant model (OR = 1.50, 95% CI = 1.11-2.03, P = 0.008). CONCLUSION: Our results suggested that TBXA2R +924C/T polymorphism is associated with asthma risk, and +795C/T polymorphism may be a risk factor for AIA. Larger-scale and well-designed studies are required to validate the association identified in the current meta-analysis.

Association between Val66Met polymorphisms in brain-derived neurotrophic factor gene and asthma risk: a meta-analysis.

OBJECTIVE: The Val66Met polymorphisms in brain-derived neurotrophic factor (BDNF) gene have been reported to be associated with asthma risk, while the results are inconclusive. Considering a single study may lack the power to provide reliable conclusion, we performed a meta-analysis to investigate the association between the Val66Met polymorphisms and asthma susceptibility. METHODS: A comprehensive literature search of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases was conducted before February 12, 2015. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. RESULTS: Six eligible studies with a total of 3501 subjects were finally included in this meta-analysis. Overall, a significantly increased risk was detected in the Val66Met G allele (G vs. A: OR 1.33, 95 % CI 1.19-1.49, P = 5.61E-07; GG vs. GA + AA: OR 1.48, 95 % CI 1.20-1.83, P = 3.14E-04; GG vs. GA: OR 1.48, 95 % CI 1.17-1.89, P = 0.001; GG vs. AA: OR 1.62, 95 % CI 1.20-2.19, P = 0.002). Moreover, stratification by ethnicity indicated marked association between the Val66Met G allele and asthma risk in Caucasians (G vs. A: OR 1.29, 95 % CI 1.12-1.49, P = 0.001; GG + GA vs. AA: OR 1.59, 95 % CI 1.03-2.46, P = 0.039; GG vs. GA + AA: OR 1.32, 95 % CI 1.11-1.57, P = 0.001; GG vs. GA: OR 1.28, 95 % CI 1.07-1.53, P = 0.007; GG vs. AA: OR 1.72, 95 % CI 1.11-2.68, P = 0.015). CONCLUSION: Our present meta-analysis suggests that the Val66Met polymorphisms in BDNF gene are potentially associated with asthma risk in Caucasians. Further well-designed case-control studies with larger sample size and more ethnic groups are needed to confirm these conclusions.

Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 ± 2.6 mmHg and right ventricle hypertrophy index to 53.4 ± 5.3% (P < 0.05 versus control) in rats, these were accompanied with significantly increased proliferation and reduced apoptosis of pulmonary vascular cells as well as pulmonary arteries remodeling. Treatment of PAH model with specific Notch inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 ± 1.3 mmHg and right ventricle hypertrophy index to 33.5 ± 2.6% (P < 0.05 versus PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells as well as inhibited pulmonary arteries remodeling. Our results further indicated that level of Notch3 protein and NICD3 were increased in MCT-induced model of PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced these changes. Our results suggest that Notch3 signaling activation stimulated pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1 reduction, and Notch3 might be a new target to treat PAH.

MPTN: A message-passing transformer network for drug repurposing from knowledge graph.

Drug repurposing (DR) based on knowledge graphs (KGs) is challenging, which uses knowledge graph reasoning models to predict new therapeutic pathways for existing drugs. With the rapid development of computing technology and the growing availability of validated biomedical data, various knowledge graph-based methods have been widely used to analyze and process complex and novel data to discover new indications for given drugs. However, existing methods need to be improved in extracting semantic information from contextual triples of biomedical entities. In this study, we propose a message-passing transformer network named MPTN based on knowledge graph for drug repurposing. Firstly, CompGCN is used as precoder to jointly aggregate entity and relation embeddings. Then, to fully capture the semantic information of entity context triples, the message propagating transformer module is designed. The module integrates the transformer into the message passing mechanism and incorporates the attention weight information of computing entity context triples into the entity embedding to update the entity embedding. Next, the residual connection is introduced to retain information as much as possible and improve prediction accuracy. Finally, MPTN utilizes the InteractE module as the decoder to obtain heterogeneous feature interactions in entity and relation representations and predict new pathways for drug treatment. Experiments on two datasets show that the model is superior to the existing knowledge graph embedding (KGE) learning methods.

Extraction of Proteins from Soil.

Soil metaproteomics could explore the proteins involved in life activities and their abundance in the soils to overcome the difficulty in pure cultures of soil microorganisms and the limitations of proteomics of pure cultures. However, the complexity and heterogeneity of soil composition, the low abundance of soil proteins, and the presence of massive interfering substances (including humic compounds) generally lead to an extremely low extraction efficiency of soil proteins. Therefore, the efficient extraction of soil proteins is a prerequisite and bottleneck problem in soil metaproteomics. In this chapter, a soil protein extraction method suitable for most types of soils with low cost and enabling simple operation (about 150 µg protein can be extracted from 5.0 g soil) is described. The quantity and purity of the extracted soil proteins could meet the requirements for further analysis using routine mass spectrometry-based proteomics.

Fungal Secretomics Through iTRAQ-Based Analysis.

Our understanding of how fungi respond and adapt to external environments can be increased by the comprehensive data sets of fungal-secreted proteins. Fungi produce a variety of secreted proteins, and environmental conditions can easily influence the fungal secretome. However, the low abundance of secreted proteins and their post-translational modifications make protein extraction more challenging. Hence, the enrichment of secreted proteins is a crucial procedure for secretome analysis. This chapter illustrates a protocol for iTRAQ-based quantitative secretome analysis describing the example of fungi exposed to different environmental conditions. The fungal-secreted proteins can be extracted by combining ultrafiltration and TCA-acetone precipitation. Subsequently, the secreted proteins can be identified and quantified by the iTRAQ-based quantitative proteomics approach.

The association between low serum calcium level and new-onset atrial fibrillation after coronary artery bypass grafting.

OBJECTIVES: This study aims to investigate the relationship between serum calcium (SC) levels and the incidence of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass graft surgery. METHODS: This retrospective, observational cohort study consecutively enrolled patients undergoing isolated coronary artery bypass grafting in Beijing Anzhen Hospital from January 2018 to December 2021. Patients with a previous history of atrial fibrillation or atrial flutter or requiring concomitant cardiac surgery were excluded. A logistic regression model was used to determine predictors of POAF. Multivariable adjustment, inverse probability of treatment weighting and propensity score matching were used to adjust for confounders. Moreover, we conducted univariable and multivariable logistic regression analyses on preoperative and postoperative SC and ionized SC levels. RESULTS: The analysis encompassed 12 293 patients. The POAF rate was significantly higher in patients with low SC level than those without (1379 [33.9%] vs 2375 [28.9%], P < 0.001). Low SC level was associated with an increased odds ratio of POAF (odds ratio [95% confidence interval]: 1.27 [1.18-1.37], P < 0.001). Inverse probability of treatment weighting and propensity score matching analyses confirmed the results. The increased POAF rate in low SC level group still existed among subgroup analysis based on different age, sex, body mass index, hypertension, hyperlipidaemia, CHA2DS2-VASc and magnesium. CONCLUSIONS: Low SC level indicates elevated POAF risk in patients undergoing isolated coronary artery bypass graft surgery even after the adjustment for age, sex, cardiovascular risk factors, echocardiographic parameters and laboratory markers.

Postoperative acute kidney injury increases short- and long-term death risks in elderly patients (≥ 75 years old) undergoing coronary artery bypass graft surgery.

PURPOSE: To explore the incidence of postoperative acute kidney injury (AKI) after coronary artery bypass grafting (CABG) in elderly Chinese patients (≥ 75 years old) and its impacts on the short- and long-term prognosis. METHODS: A total of 493 patients aged 75-88 years old who underwent CABG from two medical centers between January 2006 and October 2021 were involved. Perioperative (preoperative and 7 days after operation) serum creatinine (Scr) levels were measured in all the enrolled patients. Univariate and multivariate logistic regression analyses were conducted to explore the independent risk factors of postoperative in-hospital mortality. Kaplan-Meier curves and COX model were used to test the risk factors of all-cause death during follow-up. Propensity score matching was used to balance differences between AKI and control groups. The primary outcome event was in-hospital death, and the secondary outcome was all-cause death during follow-up. RESULTS: The 198 patients were diagnosed with postoperative AKI. Intra-aortic balloon pump (IABP), cardiopulmonary bypass, and postoperative AKI were independent risk factors of in-hospital death. Gender, New York Heart Association Classification, preoperative eGFR, last eGFR within 7 days after operation, postoperative AKI, and postoperative renal function all impacted long-term prognosis. After 1:1 matching, 190 patients were included in the AKI and control groups. Use of IABP, use of cardiopulmonary bypass, and occurrence of postoperative AKI were still independent risk factors of in-hospital death. Preoperative eGFR, last eGFR within 7 days after operation, postoperative AKI and postoperative renal function all impacted long-term prognosis. CONCLUSION: The incidence of postoperative AKI in elderly patients undergoing CABG is high, and postoperative AKI is an independent risk factor of both short- and long-term postoperative prognosis.